作者
Kathryn S Burch, Kangcheng Hou, Yi Ding, Yifei Wang, Steven Gazal, Huwenbo Shi, Bogdan Pasaniuc
发表日期
2022/4/7
期刊
The American Journal of Human Genetics
卷号
109
期号
4
页码范围
692-709
出版商
Elsevier
简介
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 pairs) have heritability exclusively from rare variants. Of these 327 gene-trait pairs, 114 (35%) were not detected by …
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