Abstract:
:Understanding 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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Cirulli ET,White S,Read RW,Elhanan G,Metcalf WJ,Tanudjaja F,Fath DM,Sandoval E,Isaksson M,Schlauch KA,Grzymski JJ,Lu JT,Washington NLdoi
10.1038/s41467-020-14288-ysubject
Has Abstractpub_date
2020-01-28 00:00:00pages
542issue
1issn
2041-1723pii
10.1038/s41467-020-14288-yjournal_volume
11pub_type
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