{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Burch KS"],"funding":["NIMH NIH HHS","NHGRI NIH HHS"],"pagination":["692-709"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9069080"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["109(4)"],"pubmed_abstract":["Recent works have shown that SNP heritability-which is dominated by low-effect common variants-may not be the most relevant quantity for localizing high-effect/critical disease genes. Here, we introduce methods to estimate the proportion of phenotypic variance explained by a given assignment of SNPs to a single gene (\"gene-level heritability\"). We partition gene-level heritability by minor allele frequency (MAF) to find genes whose gene-level heritability is explained exclusively by \"low-frequency/rare\" variants (0.5% ≤ MAF < 1%). Applying our method to ∼16K protein-coding genes and 25 quantitative traits in the UK Biobank (N = 290K \"White British\"), we find that, on average across traits, ∼2.5% of nonzero-heritability genes have a rare-variant component and only ∼0.8% (327 gene-trait pair"],"journal":["American journal of human genetics"],"pubmed_title":["Partitioning gene-level contributions to complex-trait heritability by allele frequency identifies disease-relevant genes."],"pmcid":["PMC9069080"],"funding_grant_id":["R01 MH115676","R01 HG006399","R01 HG009120"],"pubmed_authors":["Pasaniuc B","Hou K","Ding Y","Burch KS","Gazal S","Wang Y","Shi H"],"additional_accession":[]},"is_claimable":false,"name":"Partitioning gene-level contributions to complex-trait heritability by allele frequency identifies disease-relevant genes.","description":"Recent works have shown that SNP heritability-which is dominated by low-effect common variants-may not be the most relevant quantity for localizing high-effect/critical disease genes. Here, we introduce methods to estimate the proportion of phenotypic variance explained by a given assignment of SNPs to a single gene (\"gene-level heritability\"). We partition gene-level heritability by minor allele frequency (MAF) to find genes whose gene-level heritability is explained exclusively by \"low-frequency/rare\" variants (0.5% ≤ MAF < 1%). Applying our method to ∼16K protein-coding genes and 25 quantitative traits in the UK Biobank (N = 290K \"White British\"), we find that, on average across traits, ∼2.5% of nonzero-heritability genes have a rare-variant component and only ∼0.8% (327 gene-trait pair","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-19T17:36:47.171Z","creation":"2025-04-19T17:36:47.171Z"},"accession":"S-EPMC9069080","cross_references":{"pubmed":["35271803"],"doi":["10.1016/j.ajhg.2022.02.012"]}}