Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts-Reference-Cited by-同舟云学术

Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts

Published:2020-01-28 Issue:1 Volume:11 Page:
ISSN:2041-1723
Container-title:Nature Communications
language:en
Short-container-title:Nat Commun

Author:

Cirulli Elizabeth T.^ORCID,White Simon^ORCID,Read Robert W.^ORCID,Elhanan Gai,Metcalf William J.,Tanudjaja Francisco^ORCID,Fath Donna M.,Sandoval Efren,Isaksson Magnus,Schlauch Karen A.,Grzymski Joseph J.,Lu James T.,Washington Nicole L.

Abstract

AbstractUnderstanding the impact of rare variants is essential to understanding human health. We analyze rare (MAF < 0.1%) variants against 4264 phenotypes in 49,960 exome-sequenced individuals from the UK Biobank and 1934 phenotypes (1821 overlapping with UK Biobank) in 21,866 members of the Healthy Nevada Project (HNP) cohort who underwent Exome + sequencing at Helix. After using our rare-variant-tailored methodology to reduce test statistic inflation, we identify 64 statistically significant gene-based associations in our meta-analysis of the two cohorts and 37 for phenotypes available in only one cohort. Singletons make significant contributions to our results, and the vast majority of the associations could not have been identified with a genotyping chip. Our results are available for interactive browsing in a webapp (https://ukb.research.helix.com). This comprehensive analysis illustrates the biological value of large, deeply phenotyped cohorts of unselected populations coupled with NGS data.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry

Link

http://www.nature.com/articles/s41467-020-14288-y.pdf

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