Ultrarare variants drive substantial cis heritability of human gene expression.
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ABSTRACT:
SUBMITTER: Hernandez RD
PROVIDER: S-EPMC6730564 | biostudies-literature | 2019 Sep
REPOSITORIES: biostudies-literature
Publications
Ultrarare variants drive substantial cis heritability of human gene expression.
Hernandez Ryan D RD Uricchio Lawrence H LH Hartman Kevin K Ye Chun C Dahl Andrew A Zaitlen Noah N
Nature genetics 20190902 9
The vast majority of human mutations have minor allele frequencies under 1%, with the plurality observed only once (that is, 'singletons'). While Mendelian diseases are predominantly caused by rare alleles, their cumulative contribution to complex phenotypes is largely unknown. We develop and rigorously validate an approach to jointly estimate the contribution of all alleles, including singletons, to phenotypic variation. We apply our approach to transcriptional regulation, an intermediate betwe ...[more]
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