Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets – Nature.com

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Sullivan, P. F. & Geschwind, D. H. Defining the genetic, genomic, cellular, and diagnostic architectures of psychiatric disorders. Cell 177, 162183 (2019).

Article CAS PubMed PubMed Central Google Scholar

de Leeuw, C. A., Neale, B. M., Heskes, T. & Posthuma, D. The statistical properties of gene-set analysis. Nat. Rev. Genet. 17, 353364 (2016).

Article PubMed Google Scholar

Subramanian, A. et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl Acad. Sci. USA 102, 15545 (2005).

Article CAS PubMed PubMed Central Google Scholar

Ashburner, M. et al. Gene Ontology: tool for the unification of biology. Nat. Genet. 25, 2529 (2000).

Article CAS PubMed PubMed Central Google Scholar

Koopmans, F. et al. SynGO: an evidence-based, expert-curated knowledge base for the synapse. Neuron 103, 217234.e4 (2019).

Article CAS PubMed PubMed Central Google Scholar

Hill, W. D. et al. A combined analysis of genetically correlated traits identifies 187 loci and a role for neurogenesis and myelination in intelligence. Mol. Psychiatry 24, 169181 (2019).

Article CAS PubMed Google Scholar

Howard, D. M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat. Neurosci. 22, 343352 (2019).

Article CAS PubMed PubMed Central Google Scholar

Trubetskoy, V. et al. Mapping genomic loci implicates genes and synaptic biology in schizophrenia. Nature 604, 502508 (2022).

Article CAS PubMed PubMed Central Google Scholar

de Leeuw, C. A., Mooij, J. M., Heskes, T. & Posthuma, D. MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput. Biol. 11, e1004219 (2015).

Article PubMed PubMed Central Google Scholar

Simillion, C., Liechti, R., Lischer, H. E. L., Ioannidis, V. & Bruggmann, R. Avoiding the pitfalls of gene set enrichment analysis with SetRank. BMC Bioinform. 18, 151 (2017).

Article Google Scholar

Finucane, H. K. et al. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47, 12281235 (2015).

Article CAS PubMed PubMed Central Google Scholar

Goeman, J. J. & Bhlmann, P. Analyzing gene expression data in terms of gene sets: methodological issues. Bioinformatics 23, 980987 (2007).

Article CAS PubMed Google Scholar

Tashman, K. C., Cui, R., OConnor, L. J., Neale, B. M. & Finucane, H. K. Significance testing for small annotations in stratified LD-Score regression. Preprint at medRxiv https://doi.org/10.1101/2021.03.13.21249938 (2021).

Speed, D., Cai, N., Johnson, M. R., Nejentsev, S. & Balding, D. J. Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49, 986992 (2017).

Article CAS PubMed PubMed Central Google Scholar

Zabad, S., Ragsdale, A. P., Sun, R., Li, Y. & Gravel, S. Assumptions about frequency-dependent architectures of complex traits bias measures of functional enrichment. Genet. Epidemiol. 45, 621632 (2021).

Article CAS PubMed Google Scholar

Frei, O. et al. Bivariate causal mixture model quantifies polygenic overlap between complex traits beyond genetic correlation. Nat. Commun. 10, 2417 (2019).

Article PubMed PubMed Central Google Scholar

Holland, D. et al. Beyond SNP heritability: polygenicity and discoverability of phenotypes estimated with a univariate Gaussian mixture model. PLoS Genet. 16, e1008612 (2020).

Article CAS PubMed PubMed Central Google Scholar

Shadrin, A. A. et al. Phenotype-specific differences in polygenicity and effect size distribution across functional annotation categories revealed by AI-MiXeR. Bioinformatics 36, 47494756 (2020).

Article CAS PubMed PubMed Central Google Scholar

Holland, D. et al. The genetic architecture of human complex phenotypes is modulated by linkage disequilibrium and heterozygosity. Genetics 217, iyaa046 (2021).

Article PubMed PubMed Central Google Scholar

Kingma, D.P. & Ba, J. L. Adam: a method for stochastic optimization. arXiv (2014).

Chen, J. et al. The trans-ancestral genomic architecture of glycemic traits. Nat. Genet. 53, 840860 (2021).

Article CAS PubMed PubMed Central Google Scholar

Clarke, T. K. et al. Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112117). Mol. Psychiatry 22, 13761384 (2017).

Article CAS PubMed PubMed Central Google Scholar

de Lange, K. M. et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease. Nat. Genet. 49, 256261 (2017).

Article PubMed PubMed Central Google Scholar

Evangelou, E. et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat. Genet. 50, 14121425 (2018).

Article CAS PubMed PubMed Central Google Scholar

Hautakangas, H. et al. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat. Genet. 54, 152160 (2022).

Article CAS PubMed PubMed Central Google Scholar

Mahajan, A. et al. Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat. Genet. 50, 15051513 (2018).

Article CAS PubMed PubMed Central Google Scholar

Mishra, A. et al. Stroke genetics informs drug discovery and risk prediction across ancestries. Nature 611, 115123 (2022).

Article CAS PubMed PubMed Central Google Scholar

Okbay, A. et al. Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals. Nat. Genet. 54, 437449 (2022).

Article CAS PubMed PubMed Central Google Scholar

Savage, J. E. et al. Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence. Nat. Genet. 50, 912919 (2018).

Article CAS PubMed PubMed Central Google Scholar

Shah, S. et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure. Nat. Commun. 11, 163 (2020).

Article CAS PubMed PubMed Central Google Scholar

The, C.-H.G.I. The COVID-19 Host Genetics Initiative, a global initiative to elucidate the role of host genetic factors in susceptibility and severity of the SARS-CoV-2 virus pandemic. Eur. J. Hum. Genet. 28, 715718 (2020).

Article Google Scholar

Watanabe, K. et al. A global overview of pleiotropy and genetic architecture in complex traits. Nat. Genet. 51, 13391348 (2019).

Article CAS PubMed Google Scholar

Wightman, D. P. et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimers disease. Nat. Genet. 53, 12761282 (2021).

Article CAS PubMed PubMed Central Google Scholar

Wuttke, M. et al. A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nat. Genet. 51, 957972 (2019).

Article CAS PubMed PubMed Central Google Scholar

Yengo, L. et al. Meta-analysis of genome-wide association studies for height and body mass index in ~ 700000 individuals of European ancestry. Hum. Mol. Genet. 27, 36413649 (2018).

Article CAS PubMed PubMed Central Google Scholar

Smeland, O. B., Frei, O., Dale, A. M. & Andreassen, O. A. The polygenic architecture of schizophreniarethinking pathogenesis and nosology. Nat. Rev. Neurol. 16, 366379 (2020).

Article PubMed Google Scholar

Nakazawa, K. et al. GABAergic interneuron origin of schizophrenia pathophysiology. Neuropharmacology 62, 15741583 (2012).

Article CAS PubMed Google Scholar

Stedehouder, J. & Kushner, S. A. Myelination of parvalbumin interneurons: a parsimonious locus of pathophysiological convergence in schizophrenia. Mol. Psychiatry 22, 412 (2017).

Article CAS PubMed Google Scholar

Berrandou, T.-E., Balding, D. & Speed, D. LDAK-GBAT: fast and powerful gene-based association testing using summary statistics. Am. J. Hum. Genet. 110, 2329 (2023).

Article CAS PubMed Google Scholar

Gazal, S. et al. Linkage disequilibrium-dependent architecture of human complex traits shows action of negative selection. Nat. Genet. 49, 14211427 (2017).

Article CAS PubMed PubMed Central Google Scholar

Moon, A. L., Haan, N., Wilkinson, L. S., Thomas, K. L. & Hall, J. CACNA1C: association with psychiatric disorders, behavior, and neurogenesis. Schizophr. Bull. 44, 958965 (2018).

Article PubMed PubMed Central Google Scholar

Singh, T. et al. Rare coding variants in ten genes confer substantial risk for schizophrenia. Nature 604, 509516 (2022).

Article CAS PubMed PubMed Central Google Scholar

Howes, O. D. & Kapur, S. The dopamine hypothesis of schizophrenia: version IIIthe final common pathway. Schizophr. Bull. 35, 549562 (2009).

Article PubMed PubMed Central Google Scholar

Fusar-Poli, P. & Meyer-Lindenberg, A. Striatal presynaptic dopamine in schizophrenia, part II: meta-analysis of [18F/11C]-DOPA PET studies. Schizophr. Bull. 39, 3342 (2013).

Article PubMed Google Scholar

Huhn, M. et al. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet 394, 939951 (2019).

Article CAS PubMed PubMed Central Google Scholar

Harrison, P. J. Schizophrenia susceptibility genes and neurodevelopment. Biol. Psychiatry 61, 11191120 (2007).

Article PubMed Google Scholar

Burch, K. S. et al. Partitioning gene-level contributions to complex-trait heritability by allele frequency identifies disease-relevant genes. Am. J. Hum. Genet. 109, 692709 (2022).

Article CAS PubMed PubMed Central Google Scholar

Yao, D. W., OConnor, L. J., Price, A. L. & Gusev, A. Quantifying genetic effects on disease mediated by assayed gene expression levels. Nat. Genet. 52, 626633 (2020).

Article CAS PubMed PubMed Central Google Scholar

Siewert-Rocks, K. M., Kim, S. S., Yao, D. W., Shi, H. & Price, A. L. Leveraging gene co-regulation to identify gene sets enriched for disease heritability. Am. J. Hum. Genet. 109, 393404 (2022).

Article CAS PubMed PubMed Central Google Scholar

Gusev, A. et al. Integrative approaches for large-scale transcriptome-wide association studies. Nat. Genet. 48, 245252 (2016).

Article CAS PubMed PubMed Central Google Scholar

Zhu, X. & Stephens, M. Large-scale genome-wide enrichment analyses identify new trait-associated genes and pathways across 31 human phenotypes. Nat. Commun. 9, 4361 (2018).

Article PubMed PubMed Central Google Scholar

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Improved functional mapping of complex trait heritability with GSA-MiXeR implicates biologically specific gene sets - Nature.com

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