Category Archives: Genetics

Bordeaux Population Health Research Center, University of Bordeaux, Inserm, UMR 1219, Bordeaux, France

Aniket Mishra,Quentin Le Grand,Ilana Caro,Constance Bordes,David-Alexandre Trgout,Marine Germain,Christophe Tzourio,Jean-Franois Dartigues,Sara Kaffashian,Quentin Le Grand,Florence Saillour-Glenisson&Stephanie Debette

Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany

Rainer Malik,Marios K. Georgakis,Steffen Tiedt&Martin Dichgans

Iwate Tohoku Medical Megabank Organization, Iwate Medical University, Iwate, Japan

Tsuyoshi Hachiya,Makoto Sasaki,Atsushi Shimizu,Yoichi Sutoh,Kozo Tanno&Kenji Sobue

Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia

Tuuli Jrgenson,Kristi Krebs,Kaido Lepik,Tnu Esko,Andres Metspalu,Reedik Mgi,Mari Nelis&Lili Milani

Institute of Mathematics and Statistics, University of Tartu, Tartu, Estonia

Tuuli Jrgenson

Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan

Shinichi Namba,Takahiro Konuma&Yukinori Okada

Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA

Daniel C. Posner,Kelly Cho,Yuk-Lam Ho&Jennifer E. Huffman

TIMI Study Group, Boston, MA, USA

Frederick K. Kamanu,Nicholas A. Marston,Marc S. Sabatine&Christian T. Ruff

Division of Cardiovascular Medicine, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA

Frederick K. Kamanu,Nicholas A. Marston,Marc S. Sabatine&Christian T. Ruff

Division of Molecular Pathology, Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan

Masaru Koido,Takayuki Morisaki&Yoishinori Murakami

Laboratory of Complex Trait Genomics, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

Masaru Koido,Mingyang Shi,Yunye He&Yoichiro Kamatani

Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA

Marios K. Georgakis,Livia Parodi,Jonathan Rosand,Christopher D. Anderson,Ernst Mayerhofer&Christopher D. Anderson

Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA

Marios K. Georgakis,Livia Parodi,Phil L. de Jager,Jonathan Rosand,Christopher D. Anderson,Guido J. Falcone,Phil L. de Jager,Ernst Mayerhofer&Christopher D. Anderson

Laboratory of Clinical Genome Sequencing, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo, Japan

Yi-Ching Liaw&Koichi Matsuda

Department of Public Health and Institute of Public Health, Chung Shan Medical University, Taichung, Taiwan

Yi-Ching Liaw,Pei-Hsin Chen&Yung-Po Liaw

Department of Internal Medicine, University of Turku, Turku, Finland

Felix C. Vaura&Teemu J. Niiranen

Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Turku, Finland

Felix C. Vaura&Teemu J. Niiranen

Nuffield Department of Population Health, University of Oxford, Oxford, UK

Kuang Lin,Zhengming Chen,Cornelia M. van Duijn,Robert Clarke,Rory Collins,Richard Peto,Yiping Chen,Zammy Fairhurst-Hunter,Michael Hill,Alfred Pozarickij,Dan Schmidt,Becky Stevens,Iain Turnbull,Iona Y. Millwood,Keum Ji Jung&Robin G. Walters

Department of Research and Innovation, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway

Bendik Slagsvold Winsvold,Ingrid Heuch,Linda M. Pedersen,Amy E. Martinsen,Espen S. Kristoffersen&John-Anker Zwart

K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

Bendik Slagsvold Winsvold,Sigrid Brte,Kristian Hveem,Ben M. Brumpton,Jonas B. Nielsen,Maiken E. Gabrielsen,Anne H. Skogholt,Ben M. Brumpton,Maiken E. Gabrielsen,Amy E. Martinsen,Jonas B. Nielsen,Kristian Hveem,Laurent F. Thomas&John-Anker Zwart

Department of Neurology, Oslo University Hospital, Oslo, Norway

Bendik Slagsvold Winsvold&Anne H. Aamodt

Department of Biostatistics, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA

Vinodh Srinivasasainagendra,Hemant K. Tiwari&George Howard

Department of Neurology and Cerebrovascular Disease Center, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea

Hee-Joon Bae

Rajendra Institute of Medical Sciences, Ranchi, India

Ganesh Chauhan,Amit Kumar&Kameshwar Prasad

Thrombosis and Atherosclerosis Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton, Ontario, Canada

Michael R. Chong&Guillaume Par

Department of Pathology and Molecular Medicine, Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada

Michael R. Chong&Guillaume Par

Department of Neurology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland

Liisa Tomppo,Jukka Putaala,Gerli Sibolt,Nicolas Martinez-Majander,Sami Curtze,Marjaana Tiainen,Janne Kinnunen&Daniel Strbian

Center for Genomic and Precision Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria

Rufus Akinyemi,Abiodun M. Adeoye&Mayowa O. Owolabi

Neuroscience and Ageing Research Unit Institute for Advanced Medical Research and Training, College of Medicine, University of Ibadan, Ibadan, Nigeria

Rufus Akinyemi

Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Gennady V. Roshchupkin,Maria J. Knol,Cornelia M. van Duijn,Najaf Amin,Sven J. van der Lee,Mohsen Ghanbari,Mohammad K. Ikram&Mohammad A. Ikram

Department of Radiology and Nuclear Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands

Gennady V. Roshchupkin

The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Naomi Habib&Anael Cain

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA

Yon Ho Jee

Department of Clinical Biochemistry, Copenhagen University HospitalRigshospitalet, Copenhagen, Denmark

Jesper Qvist Thomassen,Anne Tybjrg-Hansen,Marianne Benn&Ruth Frikke-Schmidt

Department of Molecular and Functional Genomics, Weis Center for Research, Geisinger Health System, Danville, VA, USA

Vida Abedi&Jiang Li

Department of Public Health Sciences, College of Medicine, The Pennsylvania State University, State College, PA, USA

Vida Abedi

Stroke Pharmacogenomics and Genetics Laboratory, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain

Jara Crcel-Mrquez,Nuria P. Torres-Aguila,Natalia Cullell,Elena Muio,Cristina Gallego-Fabrega,Miquel Lleds,Laia Lluci-Carol&Israel Fernndez-Cadenas

Departament de Medicina, Universitat Autnoma de Barcelona, Barcelona, Spain

Jara Crcel-Mrquez

The Danish Twin Registry, Department of Public Health, University of Southern Denmark, Odense, Denmark

Marianne Nygaard&Kaare Christensen

Department of Clinical Genetics, Odense University Hospital, Odense, Denmark

Marianne Nygaard&Kaare Christensen

Center for Alzheimers and Related Dementias, National Institutes of Health, Bethesda, MD, USA

Hampton L. Leonard&Mike A. Nalls

Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA

Hampton L. Leonard&Mike A. Nalls

Data Tecnica International, Glen Echo, MD, USA

Hampton L. Leonard&Mike A. Nalls

Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA

Chaojie Yang,Ani Manichaikul,Stephen S. Rich,Wei Min Chen,Michle M. Sale&Wei-Min Chen

Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA

Chaojie Yang

British Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

Ekaterina Yonova-Doing,Michael Inouye&Joanna M. M. Howson

Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK

Ekaterina Yonova-Doing&Joanna M. M. Howson

Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA

Adam J. Lewis,Jing He,Seung Hoan Choi&Lisa Bastarache

Department of Surgery, University of Pennsylvania, Philadelphia, PA, USA

Renae L. Judy

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Tetsuro Ago&Takanari Kitazono

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Stroke genetics informs drug discovery and risk prediction across ancestries - Nature.com

Wondering if bad chest genes are real?

The answer is yes, sort of. But it depends on what you consider bad genes. What one person considers bad another person might consider good.

Your genes are units of genetic information that you inherit from your parents. They determine all your inherited traits from your eye color to your bone structure. Environmental factors such as nutrition, exposure to chemicals, and exercise habits can change the way some genes are expressed.

You can build muscle by engaging in resistance training. But genetic factors can influence how easily you add mass. Likewise, genetics can influence how easily you build muscle in a particular area such as your chest.

Keep reading as we take a look at how genetics affect your ability to build muscle in your chest.

Bad chest genes are subjective. Many people use the term to refer to having difficulty building muscle in their chest or difficulty building muscle with the aesthetics they want.

The bulk of your chest is made up of the bellies of your pectoralis major muscles, commonly referred to as your pecs. These muscles originate from your sternum and collar bone and insert into your upper arm.

Some people consider bad chest genes as having a large gap between their pectoralis major muscles or having an asymmetry between each side of their chest.

Do some people have better chest genetics than others? It depends on what your goals are and what you consider bad genetics.

Some people can build more muscle or build muscle at a faster rate in their chests than others. Genes play a role in the following factors:

Researchers are continuing to examine genes that play a role in building muscle mass. In one rodent study, researchers identified 47 genes linked to muscle growth.

Twin studies suggest that more than 50% of muscle fiber composition is estimated to be inherited from your parents.

Body dysmorphia is a mental health condition characterized by preoccupation with your bodys flaws. Muscle dysmorphia is a specific type of body dysmorphia characterized by a persistent worry that youre not muscular or lean.

Becoming preoccupied with the size of your chest could be a symptom of muscle dysmorphia. The Muscle Dysmorphic Disorder Inventory is often used as a testing tool with 13 questions that are scored from never to always. Some of the statements on this inventory include:

In a 2018 study, researchers compared rates of muscular dysmorphia between bodybuilders, strength athletes, and people engaged in general fitness. They found that bodybuilders reported more beliefs about being smaller and weaker than the other groups.

Learn more about how muscle dysmorphia is diagnosed and treated.

A chest gap is the separation of your pectoralis major muscles. Its normal to have a chest gap since theres no muscle body over your sternum. Some people have wider gaps than others as part of their natural anatomy, which is largely predetermined by genetics.

Its important to remember that the idea of bad genetics is subjective. If your goal is to build as much muscle as possible, you might consider bad genetics as having more trouble building muscle than other people around you.

But for some people, not adding muscle mass with training might be considered good genetics. For example, athletes in weight-class sports such as boxing or relative strength sports such as long jump need to build a large amount of strength without adding much extra weight.

You cant change your genetics, but you can change the way your genes are expressed by changing your training program. Consistently training your chest muscles can help you maximize your muscle size and strength. Some people find it helpful to work with a personal trainer who can build them a custom program to help them achieve their goals.

Some men opt to get pectoral implants, but these are primarily meant for people with birth deformities, such as pectus excavatum. People with muscle or body dysmorphia are not candidates for pectoral implants.

The best way to grow your chest is by training your chest muscle regularly. Many different exercises can target your chest. Here are some ideas:

Your genetics influence your ability to build muscle. The idea of bad genetics is subjective. If your goal is to build muscle, your genes might make it easier or harder than most other people to build muscle in general or specifically in your chest.

The best way to maximize your chest growth is to train your chest regularly. You may find it helpful to work with a personal trainer who can build you a custom program.

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About Bad Chest Genetics, and Whether You Can Fix Them - Healthline

Data collection age groupings

We downloaded gene expression data for multiple individuals and tissues from GTEx V810, which were previously aligned and processed against the hg19 human genome. Tissues were included in the analysis if they had >100 individuals in both the age 55 and <55 cohorts (Supplementary Fig.2). For a given tissue, genes were included if they had >0.1 TPM in 20% of samples and 6 reads in 20% of samples, following GTExs eQTL analysis pipeline. To compare gene expression heritability across individuals of different ages, for some analyses we split the GTEx data for each tissue into two age groups, "young" and "old," based on the median age of individuals in the full dataset, which was 55 (Supplementary Fig.1). Within each tissue dataset, we then equalized the number of individuals in the young and old groups by randomly downsampling the larger group, to ensure that our models were equally powered for the two age groups.

We analyzed existing precomputed PEER factors available from GTEx to check for correlations between these hidden covariates and age. In particular, we fit a linear regression between age and each hidden covariate and identified significant age correlations using an F-statistic (Supplementary Fig.3). Because some of the covariates were correlated with age, we generated age-independent hidden covariates of gene expression to remove batch and other confounding effects on gene expression while retaining age related variation. In particular, we first removed age contributions to gene expression by regressing gene expression on age and then ran PEER on the age-independent residual gene expression to generate 15 age-independent hidden PEER factors.

Using the binary age groups defined above, we assessed the relative significance of eQTLs in old and young individuals by carrying out separate assessment of eQTLs identified by GTEx. We report the number of genes included in analysis for each tissue (Supplementary Table1). For each gene in each tissue and each age group, we regressed the GTEx pre-normalized expression levels on the genotype of the lead SNP (identified by GTEx, MAF>0.01) using 5 PCs, 15 PEER factors, sex, PCR protocol and sequencing platform as covariates, following the GTEx best practices. We confirmed our results using both our recomputed PEER factors as well as the PEER factors provided by GTEx (Supplementary Fig.5). To test for significant differences in genetic associations with gene expression between the old and young age groups, we compared the p-value distributions between these groups for all genes and all SNPs in a given tissue using Welchs t-test. To investigate the validity of the age cutoff used for these binary age groups, we replicated the eQTL analysis using two additional age cutoffs of 45 and 65 years old. We observed the same trends in both cases; however, statistical power decreased due to smaller sample sizes in the resulting age bins, leading to a non-significant result for age cutoff 45 (Supplementary Fig.40).

To quantify differences in gene expression between individuals, we computed the pairwise distance for all pairs of individuals in an age group using the square root of Jensen-Shannon Divergence (JSD) distance metric, which measures the similarity of two probability distributions. Here we applied JSD between pairs of individuals transcriptome vectors containing the gene expression values for each gene, which we converted to a distribution by normalizing by the sum of the entries in the vector. For two individuals transcriptome distributions, the JSD can be calculated as:

$${{{{{{{rm{JSD}}}}}}}}({P}_{1},;{P}_{2})=Hleft(frac{1}{2}{P}_{1}+frac{1}{2}{P}_{2}right)-frac{1}{2}(H({P}_{1})+H({P}_{2}))$$

(1)

where Pi is the distribution for individual i and H is the Shannon entropy function:

$$H(X)=-mathop{sum }limits_{i=1}^{n}P({x}_{i}){log }_{2}(P({x}_{i}))$$

(2)

JSD is known to be a robust metric that is less sensitive to noise when calculating distance compared to traditional metrics such as Euclidean distance and correlation. It has been shown that JSD metrics and other approaches yield similar results but that JSD is more robust to outliers12. The square root of the raw JSD value follows the triangle inequality, enabling us to treat it as a distance metric.

In addition to comparing JSD between the two age groups defined above, "young" and "old", we also binned all GTEx individuals into 6 age groups, from 20 to 80 years old with an increment of 10 years. We then computed pairwise distance and average age for each pair of individuals within each bin using the square root of JSD as the distance metric. We applied a linear regression model of JSD versus age to obtain slopes, confidence intervals, and p-values.

To analyze whether cell type composition affects age-associated expression changes, we utilized the tool CIBERSORTx16 to estimate cell type composition and individual cell type expression levels in GTEx whole blood. Cell type composition estimates were computed using CIBERSORTx regular mode. Individual cell type expression level estimates were computed using CIBERSORTx high resolution mode. We then repeated our JSD and eQTL analyses on each cell type independently (see JSD and eQTL sections for details). In addition, to analyze tissue-specific differences in cell type composition, we referred to a previous study36 that computed cell type composition for different GTEx tissues using CIBERSORTx. We applied the JSD metric to each tissue, using the cell type composition vector as the distribution. Additionally, we applied the Breusch-Pagan test to compute heteroskedasicity coefficients and p-values with respect to age, after inverse logit transformation to give an approximately Gaussian distribution (Supplementary Fig.44) (see section on heteroskedastic gene expression).

We used the Breusch-Pagan test to call heteroskedastic gene expression with age. For each gene and tissue, we computed gene expression residuals by regressing out age-correlated PEER factors, other GTEx covariates, and age. To test for age-related heteroskedasticity, we squared these residuals and divided by the mean, regressed them against age, and looked at the age effect size (het). We called significantly heteroskedastic genes using a two-sided t-test with the null hypothesis that the het is zero. The Benjamini-Hochberg procedure was used to control for false positives. To determine which tissues have more genes with increasing gene expression heterogeneity with age, we compare the number of genes with positive heteroskedasticity (het > 0 and FDR<0.2) to the total of all heteroskedastic genes (FDR < 0.2). We compare this metric to the per-tissue 2-bin JSD (Supplementary Fig.41) and 6-bin JSD slope (Supplementary Fig.15).

We used a multi-SNP gene expression prediction model based on PrediXcan14 to corroborate our findings from the eQTL and JSD analyses on the two age groups, "young" and "old". For each gene in each tissue, we trained a multi-SNP model separately within each age group to predict individual-level gene expression.

$${Y}_{g,t}=mathop{sum}limits_{i}{beta }_{i,g,t}{X}_{i}+epsilon$$

(3)

Where i,g,t is the coefficient or effect size for SNP Xi in gene g and tissue t and includes all other noise and environmental effects. The regularized linear model for each gene considers dosages of all common SNPs within 1 megabase of the genes TSS as input, where common SNPs are defined as MAF > 0.05 and Hardy-Weinberg equilibrium P>0.05. We removed covariate effects on gene expression prior to model training by regressing out both GTEx covariates and age-independent PEER factors (described above). Coefficients were fit using an elastic net model which solves the problem37:

$${min }_{beta_{0},;beta }frac{1}{2N}mathop{sum }limits_{j=1}^{N}{left({Y}_{j}-{beta }_{0}-{X}_{j}^{T}beta right)}^{2}+lambda left(frac{1-alpha }{2}||beta|{|}_{2}^{2}+alpha||beta|{|}_{1}right)$$

(4)

The minimization problem contains both the error of our model predictions ({({Y}_{j}-{beta }_{0}-{X}_{j}^{T}beta )}^{2}) and a regularization term (lambda (frac{1-alpha }{2}||beta|{|}_{2}^{2}+alpha||beta|{|}_{1})) to prevent model overfitting. The elastic net regularization term incorporates both L1 (1)) and L2 ((||beta|{|}_{2}^{2})) penalties. Following PrediXcan, we weighted the L1 and L2 penalties equally using =0.514. For each model, the regularization parameter was chosen via 10-fold cross validation. The elastic net models were fit using Pythons glmnet package and R2 was evaluated using scikit-learn. From the trained models for each gene, we evaluated training set genetic R2 (or h2) for the two age groups and subtracted ({h}_{{{{{young}}}}}^{2}-{h}_{{{{{old}}}}}^{2}) to get the difference in gene expression heritability between the groups. We compared this average difference in heritability to the mean JSDoldJSDyoung and (log ({P}_{old})-log ({P}_{young})) using P-values from the eQTL analyses across genes.

To uncover linear relationships between gene expression and both age and genetics, we built a set of gene expression prediction models using both common SNPs and standardized age as input. An individuals gene expression level Y for a gene g and tissue t is modeled as:

$${Y}_{g,t}=mathop{sum}limits_{i}{beta }_{i,g,t}{X}_{i}+{beta }_{{{{{{{{rm{age}}}}}}}},g,t}A+epsilon$$

(5)

Where A is the normalized age of an individual. Coefficients were fit using elastic net regularization, as above, which sets coefficients for non-informative predictors to zero. The sign of the fitted age coefficient (age,g,t), when nonzero, reflects whether the gene in that tissue is expressed more in young (negative coefficient) or old (positive coefficient) individuals. We also evaluated the training set R2 using the fit model coefficients separately for genetics (across all SNPs in the model) and age:

$${R}_{genetics}^{2}={h}^{2}={R}^{2}({Y}_{g,t},mathop{sum}limits_{i}{beta }_{i,g,t}{X}_{i})$$

(6)

$${R}_{age}^{2}={R}^{2}({Y}_{g,t},;{beta }_{{{{{{{{rm{age}}}}}}}},g,t}A)$$

(7)

We also tested whether the age-related gene expression relationship was sex-specific by rerunning the joint model with an additional age-sex interaction term as follows:

$${Y}_{g,t}=mathop{sum}limits_{i}{beta }_{i,g,t}{X}_{i}+{beta }_{{{{{{{{rm{age}}}}}}}},g,t}A+{beta }_{{{{{{{{rm{age}}}}}}}} * {{{{{{{rm{sex}}}}}}}},g,t}A * S+epsilon$$

(8)

Where agesex,g,t is the additional model weight for the age-sex interaction term and S is the binary sex of the GTEx individual. The R2 of age, genetics, and the age-sex interaction term are evaluated as before by determining the variance explained by each term in the model. We compared the ({R}_{age}^{2}) between the models including or excluding the age-sex interaction term (Supplementary Fig.26). We also compared the tissue-averaged variance explained by age and the age-sex interaction term. Finally, to check the consistency of tissue-specific gene expression heritability estimates from our model and the original PrediXcan model trained on GTEx data, we evaluate Pearsons r between our heritability estimates and those of PrediXcan (Supplementary Fig.20), using heritability estimates from the original PrediXcan model available in PredictDB.

We evaluated the variability of age and genetic associations across tissues using a measure of tissue specificity for age and genetic R238. We measured the tissue-specificity of a gene gs variance explained ({R}_{g}^{2}) using the following metric:

$${S}_{g}=frac{mathop{sum }nolimits_{t=1}^{n}left(1-frac{{R}_{g,t}^{2}}{{R}_{g,max }^{2}}right)}{n-1}$$

(9)

Where n is the total number of tissues, ({R}_{g,t}^{2}) is the variance explained by either age or genetics for the gene g in tissue t and ({R}_{g,max }^{2}) is the maximum variance explained for g over all tissues. This metric can be thought of as the average reduction in variance explained relative to the maximum variance explained across tissues for a given gene. The metric ranges from 0 to 1, with 0 representing ubiquitously high genetic or age R2 and 1 representing only one tissue with nonzero genetic or age R2 for a given gene. We calculate Sg separately for ({R}_{{{{{{{{rm{age}}}}}}}}}^{2}) and ({R}_{{{{{{{{rm{genetics}}}}}}}}}^{2}) across all genes.

We quantified gene constraint using the probability of loss of function intolerance (pLI) from gnomAD 2.1.122. We analyzed the relationships between pLI vs age and pLI vs heritability across genes. For these analyses, genes were only included if age or genetics were predictive of gene expression (R2>0) for that gene. For genes with R2>0, we used linear regression to determine the direction of the relationship between pLI and age or heritability for each tissue. The F-statistic was used to determine whether pLI was significantly related to these two model outputs. For pLI vs age, a significant negative slope was considered a Medawarian trend (consistent with Medawars hypothesis) and a significant positive slope a non-Medawarian trend. To test whether the non-Medawarian trends were driven by genes with higher expression, we excluded genes in the top quartile of median gene expression and repeated the analysis between pLI and age (Supplementary Fig.42). We also analyzed the evolutionary constraint metric dN/dS23 and its tissue-specific relationship with age by determining the slope and significance of the linear regression, as above.

We quantified the per-gene and per-tissue cancer somatic mutation frequency using data from the COSMIC cancer browser26. For each tissue, we selected the closest cancer type as noted in Supplementary Data5 and downloaded the number of mutated samples (tumor samples with at least one somatic mutation within the gene) and the total number of samples for all genes. We computed the cancer somatic mutation frequency by dividing the number of mutated samples by the total number of samples. For each tissue, we plotted the genes age vs its cancer somatic mutation frequency for all genes with>200 tumor samples. We report the slope and significance of the relationship between age and cancer somatic mutation frequency for each tissue. To determine whether age-dependent gene expression heteroskedasticity is related to a genes involvement in cancer (Supplementary Fig.43), we also plotted each genes heteroskedasticity effect size vs the cancer somatic mutation frequency for all genes with >200 tumor samples and moderately significant heteroskedasticity (FDR<0.2). Tissues with5 genes meeting these criteria are not plotted.

To explore the non-Medawarian trend in some tissues, we assessed the distribution of age across Medawarian and non-Medawarian tissues for genes within each of the 50 MSigDB hallmark pathways24. Significant differences between the distributions were called using a t-test, and p-values were adjusted for multiple hypothesis testing using a Benjamini-Hochberg correction.

Further information on research design is available in theNature Research Reporting Summary linked to this article.

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Tissue-specific impacts of aging and genetics on gene expression patterns in humans - Nature.com

Establishing a new field of science to answer the question of what makes humans unique from our extinct relatives has earned Svante Pbo the Nobel Prize in physiology or medicine.

Humanity has always been intrigued by its origins. Where did we come from and how are we related to those who came before us? What makes us different from hominins that went extinct? said Anna Wedell, a member of the Nobel Assembly at the Karolinska Institute in Stockholm that announced the prize on October 3.

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Before Pbos work, archaeologists and paleontologists studied bones and artifacts to learn about human evolution. But the surface study of those relics couldnt answer some fundamental questions about the genetic changes that led humans to thrive while other ancient hominids went extinct. Pbo, a geneticist at the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany, worked out a way to extract and analyze DNA from ancient bones (SN: 11/15/06). That led to uncovering small genetic differences between humans and extinct human relatives.

Getting DNA from ancient bones was once considered impossible, says Leslie Vosshall, a neuroscientist at the Rockefeller University in New York City, who is the vice president and chief scientific officer at the Howard Hughes Medical Institute. DNA breaks down over time, so many scientists thought that there would be none remaining in fossils tens of thousands of years old. Not to mention that DNA from bacteria and other microbes and from living people contaminate the ancient genetic material. Yet Pbo managed to stitch together tiny fragments of Neandertal DNA into readable sequences. He started with DNA from mitochondria, the energy-generating organelles inside cells. Then, he assembled a complete genetic instruction book, or genome, for a Neandertal.

Over the years Vosshall watched as Pbo presented snippets of DNA from old bones at scientific meetings. Nobody believed him. Everyone thought it was contamination or broken stuff from living people. Just the mere fact that he did it was so improbable. That he was able to get the complete genome sequence of a Neandertal was viewed, even up until he did it, as an absolutely impossible feat.

On a technical basis, the prize is also richly deserved, she says.

Noted Nils-Gran Larsson, vice chairman of the Nobel committee: This is a very fundamental, big discovery Over the years to come, [this] will give huge insights into human physiology.

Pbos work established the field of paleogenomics. He always pushed the frontiers of evolutionary anthropology, says Ludovic Orlando, a molecular archaeologist at the Centre for Anthropobiology and Genomics of Toulouse in France.

Pbo said that when he got the news of his win, he thought at first it was an elaborate prank by the people in his research group, but soon realized it was the real deal. The thing that is amazing to me is that we now have some ability to go back in time and actually follow genetic history and genetic changes over time, he said in a news conference several hours after the prize was announced.

Pbo and colleagues have made surprising discoveries about human evolution from studying ancient DNA. For instance, they learned that humans and our extinct cousins, Neandertals, had children together. That discovery came as a shock to even people who had been looking for signs of interbreeding (SN: 5/6/10). Evidence of that mixing can still be found in many humans today (SN: 10/10/17).

Pbos study of a finger bone revealed a previously undiscovered extinct human relative called Denisovans (SN: 8/30/12). Like Neandertals, Denisovans interbred with humans.

DNA passed down from those extinct ancestors has influenced human health and physiology for better or worse. For instance, genetic variants inherited from Denisovans helped humans adapt to high altitude in Tibet (SN: 7/2/14). But some Neandertal DNA has been linked to a higher risk of developing some diseases, including severe COVID-19 (SN: 2/11/16; SN: 10/2/20).

His work has also delved into tiny genetic changes that may have influenced the evolution of the human brain (SN: 2/26/15). Other researchers have also applied techniques Pbo developed to study evolution and domestication of animals (SN: 7/6/17), and to learn about how ancient humans moved around the world.

Hes a singular scientist, Vosshall says.

Hes not the only one in his family to win a Nobel Prize, though. Pbos father, Sune Bergstrm, shared the medicine Nobel Prize in 1982 (SN: 10/16/82).

Pbo will take home prize money of 10 million Swedish kronor, roughly $895,000 as of October 3.

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Genetics of human evolution wins 2022 Nobel Prize in physiology or medicine - Science News Magazine

Illumina Inc. says it can read a persons entire genetic code for as little as $200 with its new sequencing machine, bringing the company within reach of its long-promised goal of the $100 genome.

Illumina on Thursday unveiled a new line of DNA sequencing machines it says are twice as fast and accurate as its earlier models. Together, those upgrades will bring the cost per genome down two-thirds from its current technology, Chief Executive Officer Francis deSouza said.

Many consumers have been introduced to their DNA through relatively low-cost tests like those marketed by 23andMe Holding Co. that analyze small snippets of the genome for clues to disease risk and ancestry. Whole-genome sequencing can provide a far clearer, more accurate view of patients genetic makeup that doctors can use to precisely identify some diseases, including certain forms of cancer and heart disease. However, the price of performing the tests, along with their interpretation, has been a barrier for many patients that companies have been trying to bridge.

More efficient machinery and materials reduce customer cost to sequencing one genome, or the complete set of genetic material, Illumina said, adding that costs would range from less than $200 per genome, with discounts for bulk use, to $240 for a higher-quality analysis. Slashing the price of reading DNA could allow the practice to move into the mainstream, where it might be used to better tailor medications or treatments to people or have other health benefits.

This will be a huge force in terms of significantly increasing accessibility to genomics in a number of ways, deSouza said in an interview ahead of the announcement. It will democratize access to genomics by allowing sequencing to be offered to hospitals and researchers at much lower prices.

Despite promises of personalized medical care for the masses, genetic data has mostly been confined to research settings in the 21 years since an international group of scientists published the first analysis of the human genome sequence, Eric Topol, founder and director of Scripps Research Translational Institute, recently wrote. Illumina sees its new sequencing machine as a way to change that. Every meaningful price drop has rapidly led to an increase in the number of people whose genes have been analyzed, deSouza said.

Illuminas new NovaSeq X series comes in two models, with the base machine costing $985,000 and a more advanced one at $1.25 million. The new sequencers also come with new features like a simpler interface that could allow people without advanced degrees to use the machines, deSouza said.

This is a crucial test for San Diego-based Illumina at a time of increased scrutiny from Wall Street. The company cut its full-year sales outlook last month, raising questions about demand. New competitors are cropping up and threatening Illuminas dominance of the sequencing market. Moreover, the companys years-long quest to acquire early-cancer detection company Grail is in limbo and facing regulatory challenges in Europe. Shares of Illumina have lost nearly half their value this year.

Already under a microscope, the company is hosting a splashy conference in its hometown this week to unveil the technology.

Investors are closely following the event for signs Illumina can change its story. Customers, mostly drug companies and research institutions, will be paying attention to price. Before the launch, nearly three dozen sequencing customers had estimated Illumina would set its prices at $280 per genome, according to a survey from Cowen analysts.

The new machines could have real financial implications for researchers who sequence large numbers of people, said Aris Baras, who leads Regeneron Pharmaceuticals Inc.s Genetics Center. Regeneron scours genetic data to discover new drug targets. Baras praised Illumina for continuously decreasing the price of sequencing, allowing Regeneron to screen about 2 million people.

Its a testament to Illuminas innovation pushing down costs and increasing output especially when they havent historically had too many competitors being able to match them, Baras said. Still, the price isnt low enough for Regeneron to switch to exclusively whole genome sequencing. The drugmaker mostly scans only genes of key interest, which costs between one-fifth and one-tenth the price of reading all of a persons genetic material.

Read the original post:
Illumina aims to push genetics beyond the lab with $200 genome - The Spokesman Review

A University of Maryland researcher was awarded $2.6 million by the U.S. Department of Energy to investigate the genetics underlying how poplar trees sense nutrients and regulate their metabolisminformation that could help farmers maximize yields of this and other plants used in biofuel production.

Dedicated biomass crops like poplar, switchgrass, miscanthus and bamboo are grown on marginal lands that are not well suited to traditional crops like corn and wheat. It pays to understand how crops grown in such conditions use the nutrients available, how they metabolize and grow tissue, and how they respond to stressful conditions like drought.

Were interested in getting more information about how biomass crops like poplar sense and utilize nutrients so we can develop more informed strategies for manipulating this system and making it more efficient, said Gary Coleman, an associate professor in the Department of Plant Science and Landscape Architecture who is leading the research.

Coleman is looking at the genes that encode for the TOR protein, one of the central components of the TOR complex. Its job is to receive signals from the molecules that sense a wide range of nutrients like carbon and nitrogen, and then relay that information to the cellular machinery that activates growth and inhibits cell death.

Mutating the TOR gene is lethal, which is why its function is not well understood. Poplar is rare in that it has two copies of the TOR gene. Coleman and his colleagues previously demonstrated that they could manipulate one copy or the other without killing the plant, and the team intends to take advantage of the duplicates to investigate how the gene works.

Colemans collaborators include Yiping Qi, an associate professor of plant science and landscape architecture at UMD, Edward Eisenstein, an associate professor at the Institute for Bioscience and Biotechnology Research at UMD, and researchers at the Michigan Technological University.

Read more here:
$2.6M DOE Grant Supports UMD-led Study on Genetics of Plant Growth - Maryland Today

The Centre for DNA Fingerprinting and Diagnostics (CDFD) here has undertaken a study to look for rare genetic diseases with samples collected from different castes, linguistic groups and regions across the country to understand their prevalence and analyse the mutations for taking up counselling for the affected groups.

CDFD director K. Thangaraj told Manthan-Samvaad 2022, the annual event of Manthan public discourse forum, on Sunday about 20 different centres across the country India involved in the study making use of animal models, and that a special lab for rare diseases has also been opened at the institute for the purpose.

The eminent geneticist disclosed that there are a lot more population-specific recessive diseases among the Indian and South Asian people because of the endogamous (intra-community) marriages and that has to be studied. If the disease-causing mutation is dominant, it will come out but in recessive mutations, it will be carried across generations and could arise in the off springs subsequently even if they are not related but belong to the same community, he explained.

Every Indian population is unique, yet has some kind of genetic affinities. If the Andamanese were the first to migrate from Africa, second batch moved to Europe and some towards North India called as Ancestral North Indians (ANI). These groups admixed within themselves and with Ancestral South Indians (ASI) 2,000-3,000 years ago before endogamous relationships became the norm 2,000 years ago. It refutes the Aryan invasion theory, but brought forth a large recessive disease base, said Dr. Thangaraj.

With many other populations like Jews and Parsis having migrated later, India becomes a complex nation in terms of genetics, and analysing gives lot more information about the genetic affinities between them. The endogamous impact on health and diseases like cardiac diseases was found to be more prevalent in South Asia, he said.

Since there are many populations suffering with rare genetic diseases, the need of the hour is to follow the Jewish method of genetic study to look for mutations and followed by counselling among the couples, to stop the further spread of the disease, he added.

Former Indian Ambassador to Saudi Arabia Talmiz Ahmed in his talk Indias western neighbours friends or foes called for a new strategic doctrine with emphasis on forging better ties with West Asia because of oil, trade, working population and huge remittances and others, Iran, Russia and even China despite difficulties, rather than leaning too much on the United States, whose influence and power has been diminishing.

Ex-Army officer and Senior Fellow at the Centre for Policy Research Sushant Singh said while the financial burden of huge defence pensions has forced the government hand in bringing out the Agnipath scheme of recruitment into armed forces, it is flawed. It could disturb the armed forces functioning and also damage the civic society later especially when there is large scale unemployment and the economy is down. Manthan trustees former chief secretary K. Madhav Rao and M.R. Vikram also spoke.

Read more:
Study on rare genetic diseases among diverse demographics in India - The Hindu

That said, its important to remember that our erotic interests are the product of many factors. On the biological side, those factors can include our genetic predispositions, unique brain chemistry, and the way our bodies are laid out.

For some people, nipples are extraordinarily sensitive, Dr. Lehmiller says. For other people, theres just no sensation whatsoever. And if your body just happens to have that heightened level of sensitivity, you might be very drawn to various forms of nipple play including more intense BDSM versions of it with nipple clamps and so forth. So I think part of it is that general sensitivity in different parts of our body. That could also have a genetic component to it.

Psychological factors such as our personalities, previous experiences, and general attitudes toward sex represent another piece of the puzzle. And there are environmental factors to considerthe cultural context that, in part, determines the partners we choose and the opportunities available to us.

Whenever were talking about sexual interests, we need to talk about it from a biopsychosocial perspective, Dr. Lehmiller says. Two people can develop the same sexual interest for very different reasons, depending on the confluence of all of these factors.

Many people can pinpoint a specific childhood experience as the source of their kink or fetish. For some, it feels like a fact of life from birth. Others find their kinks later in life through solo or partnered exploration. In Dr. Brames experience, younger generations are becoming aware of their kinks earlier in life thanks to the internet. But in some cases, the culture of silence and shame around sexual kinks can delay the discovery process by decades.

You dont necessarily realize who you are until youre in your teens or maybe even your 20s, Dr. Brame says. Or maybe even your 50s, not because its totally out of the blue. But you dont realize what kink is or what it is to be kinky. Or that some of your private sexual fantasies actually align with kink.

Often the kinks emotional and sexual resonance is reinforced through masturbation.

We know that the connection between the smell centers of the brain and the memory centers of the brain and the emotional centers of the brain are very close, Gates says. And so things that we would consider to be classic kinks, like a foot fetishor rubber or leather or things that are sensorially evocative, especially through smellcan become connected with emotional content and memories to form a kind of cycle where you smell it and you have this stimulus in this memory thats very emotional. You might reinforce that through, say, masturbation to the point where it becomes a very firm pathway in your brain.

But Gates believes some people are primed to develop a kink or fetish under the right conditions.

I interviewed this wonderful guy who considered himself a macrophile, Gates says. He liked to fantasize about giant women. And he said, Nature loads the gun and nurture pulls the trigger. I like that metaphor because it sort of explains how that worksthat you can be primed biologically and neurologically to be ready for it to happen.

Dr. Brame feels strongly that kink isnt a hobbyits a legitimate sexual identity. Throughout her life, relationships that didnt align with her kinks would inevitably fail. The kink was never explicitly discussed or cited as the reason for the breakupthat discovery would come later. But in retrospect, it makes sense that certain power dynamics werent tenable for her.

The rest is here:
Are Kinks Hereditary? What Science Says About the Genetics of Desire - Glamour

WASHINGTON Today, the Chan Zuckerberg Initiative (CZI) announced a partnership with Howard Universityand the nations three other historically Black medical colleges to further support cutting-edge scientific research to address significant gaps in genomics. CZIs Accelerate Precision Health (APH) program will award $11.5 million to Howard University's Office of Research over five years, allowing the University to expand research in the genome field, bring on renowned faculty, fund post-doctoral fellows, and support grant writing for future initiatives.

The $11.5 million award represents the latest stride toward fulfilling a key research goal outlined in the Howard Forward Office of Research strategic plan to leverage Howards genetic research to attract and mobilize resources to tackle global challenges, especially as they relate to Black populations. Black communities have been historically underrepresented in clinical trials and genetics research and today are still often excluded from medical studies. Recently, during the COVID-19 pandemic, despite Black Americans suffering a higher mortality rate than whites, many studies excluded Black participants.

To me, genetics research is more than just an academic pursuit, said Howard University President Wayne A. I. Frederick, M.D., MBA. As someone with sickle cell anemia, the study of genetics is not abstract. When I was born, people with sickle cell disease were told that they would not live beyond childhood. Today, a child born with sickle cell disease has somewhere around a 99% chance of living to adulthood. Those advances didnt happen by accident: Howard researchers have participated in every clinical trial that has led to FDA-approved medications for sickle cell disease treatment. This grant from CZI will allow us to continue to break new ground in genetics and genomics research for generations to come.

I am incredibly excited for this new venture with CZI to expand Howards important work in the fields of genomics and genetics, said Bruce Jones, Ph.D., Vice President for Research at Howard University. Research partnerships at Howard expand our understanding of issues impacting the Black community, from genetics and genomics and other STEM fields, to groundbreaking research in literature, the arts, law and other social science fields, leading to advancements in policy, medicine, and culture that benefit all communities.

For generations, Howard University has been at the forefront of genomics and genetics research, with a focus on the Black community. More than 50 years ago, Howard launched the Center for Sickle Cell Disease with the goal of providing care for patients and advancing research into sickle cell disease, the most frequent rare genetic disease, which mostly affects people of African descent. Twenty years ago, Howard launched the first large-scale collection of genetic profiles of African Americans.

Today, researchers at the National Human Genome Center at Howard University continue to work on the frontlines of genomics and genetics, including research by Dr. Angel Byrd on gene expression of Alibert Bazin syndrome and other lymphomas that disproportionately harm Black patients and Dr. Bernard Kwabi-Addos genetic research of prostate cancer disparities in Black communities.

The Howard University Accelerating Precision Health grant is led by co-principal investigators Kera Lawson, Ph.D., executive director of research development, and Pamela A.G. Clarke, MSc., director of research development in the Office of Research.

Specific initiatives at Howard to be funded by the CZI APH program include:

The new partnership will create new opportunities for cross-collaboration between Chan Zuckerberg Initiative staff and Howard faculty and students, including: the matching of Howard faculty expertise with other CZI research partners to foster joint interdisciplinary efforts and research; CZI professional development and training opportunities for Howard faculty; and opportunities for Howard students to learn new techniques outside of their home institution.

Pictured:Howard University'sDr. Marjorie C. Gondr-Lewis and team,whose NeuroPsychoPharmacology Laboratoryconductsprecision brain health research. Photo image courtesy of CZI.

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About Howard University

Founded in 1867, Howard University is a private, research university that is comprised of 14 schools and colleges. Students pursue more than 140 programs of study leading to undergraduate, graduate and professional degrees. The University operates with a commitment to Excellence in Truth and Service and has produced one Schwarzman Scholar, three Marshall Scholars, four Rhodes Scholars, 12 Truman Scholars, 25 Pickering Fellows and more than 165 Fulbright recipients. Howard also produces more on-campus African American Ph.D. recipients than any other university in the United States. For more information on Howard University, visit http://www.howard.edu.

About the Chan Zuckerberg Initiative

The Chan Zuckerberg Initiative was founded in 2015 to help solve some of societys toughestchallengesfrom eradicating disease and improving education, to addressing the needs of ourcommunities. Through collaboration, providing resources and building technology, our mission is to help build a more inclusive, just, and healthy future for everyone. For more information, please visit http://www.chanzuckerberg.com.

Media contact: Sholnn Freeman; sholnn.freeman@howard.edu

See more here:
Howard University's Office of Research Awarded $11.5 Million From Chan Zuckerberg Initiative To Advance Genomics And Genetics Research - The Dig

Centogene NV

Working together with Denali Therapeutics to accelerate data-driven precision medicine for the PD community

Rostock International Parkinson's Disease (ROPAD) Study aims to characterize the genetics of PD to establish a better understanding of the disease progression, diagnosis, and treatment

Worldwide 120 study sites marks this as the largest observational study for genetics in PD

CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, Oct. 03, 2022 (GLOBE NEWSWIRE) -- Centogene N.V. (Nasdaq: CNTG), the commercial-stage essential biodata life science partner for rare and neurodegenerative diseases, today announced reaching a significant milestone with the recruitment and genetic testing of 12,500 participants in the Rostock International Parkinson's Disease (ROPAD) Study. With more than 120 study sites around the world, CENTOGENE is leading the largest study of its kind a global observational study focused on the role of genetics in Parkinson's disease (PD). As part of the ROPAD study, CENTOGENE utilizes CentoCard, its proprietary, CE-marked dried blood spot collection kit in combination with state-of-the-art sequencing technologies to develop a first-in-class Parkinsons Disease Panel that is being used to screen participants for mutations in leucine-rich repeat kinase 2 (LRRK2) as well as other PD-associated genes. CENTOGENEs Parkinsons Disease Panel has been widely adopted by clinicians, and its use could provide vital information to allow more precise therapeutic development in the future.

Having met the initial milestone of recruiting and performing genetic testing of 10,000 participants in March 2021, CENTOGENE and Denali Therapeutics extended their partnership to recruit and test an additional 2,500 patients. In 2018, CENTOGENE entered a strategic collaboration with Denali Therapeutics for the targeted global identification of PD patients with mutations in the LRRK2 gene. The LRRK2 gene is one of the most common mutated genes in familial PD.

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Patients enrolled in ROPAD and identified with a LRRK2 mutation may be eligible for participation in future therapeutic clinical studies. CENTOGENE conducts clinical studies with biopharma partners around the world, such as Denali Therapeutics, who are currently evaluating the efficacy and safety of a small molecule, LRRK2 inhibitor, which aims to slow the progression of PD in individuals with a pathogenic mutation in LRRK2 in the LIGHTHOUSE study. More information about LIGHTHOUSE (NCT05418673) is available at ClinicalTrials.gov.

Parkinsons disease is a devastating neurodegenerative disease, and there is a significant medical need to truly unveil deeper data on PD genetics to accelerate diagnosis and personalized Parkinsons treatments, said Kim Stratton, Chief Executive Officer at CENTOGENE. In reaching such a pivotal milestone in our Parkinsons disease study, we have been able to unlock significant insights into the genetic factors which we believe together with partners, such as Denali with their therapeutics targeting LRRK2, will accelerate the development of potentially life-saving therapeutics for many PD patients around the world.

More than 10 million people worldwide are affected by Parkinsons disease, many of which are tied to genetic factors, like LRRK2, said Carole Ho, M.D., Chief Medical Officer at Denali. In combining forces with CENTOGENE, we have unlocked significant insights and are committed to working together towards a unified goal of accelerating the development of potentially life-saving therapeutics for PD patients around the world.

About ROPAD

The Rostock International Parkinson's Disease Study (ROPAD) is a global epidemiological study focusing on the role of genetics in Parkinson's disease (PD). The major goal of the study is to characterize the genetics of PD to establish a better understanding of the disease etiology, diagnosis, and severity.

CENTOGENE utilizes CentoCard, the Companys proprietary, CE-marked dried blood spot collection kit in combination with state-of-the-art sequencing technologies to screen for mutations in LRRK2 and other PD-associated genes. This is based on insights powered by the CENTOGENE Biodatabank, what the Company believes to be the worlds largest real-world data repository for rare and neurodegenerative diseases. Throughout this study, 12,500 participants from around the world have been tested over a circa three-year period.

Patients with mutations in PD genes are offered further clinical assessment in a supplementary study, Lbeck International Parkinsons Disease Project (LIPAD), conducted at the University of Lbeck where a detailed phenotyping of participants is being performed. Patients enrolled in ROPAD and identified with a LRRK2 mutation may be eligible for participation in future therapeutic clinical studies. CENTOGENE conducts clinical studies with biopharma partners around the world, such as Denali Therapeutics, who are currently developing a small molecule, LRRK2 inhibitor for the treatment of PD.

To learn more about ROPAD, visit: https://www.centogene.com/pharma/clinical-trial-support/rostock-international-parkinsons-disease-study-ropad

About Denali Therapeutics

Denali Therapeutics is a biopharmaceutical company developing a broad portfolio of product candidates engineered to cross the blood-brain barrier (BBB) for neurodegenerative diseases. Denali pursues new treatments by rigorously assessing genetically validated targets, engineering delivery across the BBB and guiding development through biomarkers that demonstrate target and pathway engagement. Denali is based in South San Francisco. For additional information, please visit http://www.denalitherapeutics.com.

About CENTOGENE

CENTOGENE (Nasdaq: CNTG) is transforming real-world clinical, genetic, and multiomic data to enable better health outcomes for patients with rare and neurodegenerative diseases. For over 15 years, CENTOGENE has been providing diagnostic insights to patients with genetic diseases through our network of nearly 30,000 active physicians. CENTOGENE now believes its Biodatabank is the worlds largest real-world data repository of corresponding patients from more than 120 countries. Simplified logistics solutions, including CentoCard for sending biosamples, and our ISO, CAP, & CLIA certified state-of-the-art multiomic reference labs offer patients rapid and reliable diagnoses to support the identification and personalization of their treatments. Ultimately, offering the best treatment for patients involves developing new or better therapies. We are de-risking orphan drug discovery and development by partnering with more than 30 biopharma in target & drug screening, clinical development, market access and expansion. CENTOGENE engages in biodata partnerships with our Biodata Licenses and Insight Reports.

To discover more about our products, pipeline, and patient-driven purpose, visitwww.centogene.comand follow us onLinkedIn

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the U.S. federal securities laws. Statements contained herein that are not clearly historical in nature are forward-looking, and the words anticipate, believe, continues, expect, estimate, intend, project, and similar expressions and future or conditional verbs such as will, would, should, could, might, can, and may, are generally intended to identify forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties, and other important factors that may cause CENTOGENEs actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, negative economic and geopolitical conditions and instability and volatility in the worldwide financial markets, possible changes in current and proposed legislation, regulations and governmental policies, pressures from increasing competition and consolidation in our industry, the expense and uncertainty of regulatory approval, including from the U.S. Food and Drug Administration, our reliance on third parties and collaboration partners, including our ability to manage growth and enter into new client relationships, our dependency on the rare disease industry, our ability to manage international expansion, our reliance on key personnel, our reliance on intellectual property protection, fluctuations of our operating results due to the effect of exchange rates, our ability to streamline cash usage, our requirement for additional financing, or other factors. For further information on the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to CENTOGENEs business in general, see CENTOGENEs risk factors set forth in CENTOGENEs Form 20-F filed on March 31, 2022, with the Securities and Exchange Commission (the SEC) and subsequent filings with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and CENTOGENEs specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Media Contact:

CENTOGENEBen LeggCorporate CommunicationsPress@centogene.com

Lennart StreibelInvestor RelationsInvestor.Relations@centogene.com

Originally posted here:
CENTOGENE Reaches 12,500 Patient Milestone in Worlds Largest Observational Study on Parkinsons Disease Genetics - Yahoo Finance