| Title: | Genome-wide rare variant analysis for thousands of phenotypes in over 70,000 exomes from two cohorts |
| Journal: | Nature Communications |
| Published: | 28 Jan 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/31992710/ |
| DOI: | https://doi.org/10.1038/s41467-020-14288-y |
| URL: | https://www.nature.com/articles/s41467-020-14288-y.pdf |
| Citations: | 123 (34 in last 2 years) as of 8 Aug 2024 |
Publication 5068
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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.</p>
13 Authors
- Elizabeth T. Cirulli
- Simon White
- Robert W. Read
- Gai Elhanan
- William J. Metcalf
- Francisco Tanudjaja
- Donna M. Fath
- Efren Sandoval
- Magnus Isaksson
- Karen A. Schlauch
- Joseph J. Grzymski
- James T. Lu
- Nicole L. Washington
Enabling scientific discoveries that improve human health