| Title: | Identifying genetic variants that affect viability in large cohorts |
| Journal: | PLoS Biol |
| Published: | 1 Sep 2017 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/28873088/ |
| DOI: | https://doi.org/10.1371/journal.pbio.2002458 |
Publication 2884
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Abstract
Our global understanding of adaptation in humans is limited to indirect statistical inferences from patterns of genetic variation, which are sensitive to past selection pressures. We introduced a method that allowed us to directly observe ongoing selection in humans by identifying genetic variants that affect survival to a given age (i.e., viability selection). We applied our approach to the GERA cohort and parents of the UK Biobank participants. We found viability effects of variants near the APOE and CHRNA3 genes, which are associated with the risk of Alzheimer disease and smoking behavior, respectively. We also tested for the joint effect of sets of genetic variants that influence quantitative traits. We uncovered an association between longer life span and genetic variants that delay puberty timing and age at first birth. We also detected detrimental effects of higher genetically predicted cholesterol levels, body mass index, risk of coronary artery disease (CAD), and risk of asthma on survival. Some of the observed effects differ between males and females, most notably those at the CHRNA3 gene and variants associated with risk of CAD and cholesterol levels. Beyond this application, our analysis shows how large biomedical data sets can be used to study natural selection in humans.1 Author
- Mostafavi H et al.
1 Application
| Application ID | Title |
|---|---|
| 11138 | Genomic and evolutionary analyses of common disease in a large cohort |
Enabling scientific discoveries that improve human health