Mar 1, 2016

Fast Principal-Component Analysis Reveals Convergent Evolution of ADH1B in Europe and East Asia

American Journal of Human Genetics
Kevin J GalinskyAlkes L Price

Abstract

Searching for genetic variants with unusual differentiation between subpopulations is an established approach for identifying signals of natural selection. However, existing methods generally require discrete subpopulations. We introduce a method that infers selection using principal components (PCs) by identifying variants whose differentiation along top PCs is significantly greater than the null distribution of genetic drift. To enable the application of this method to large datasets, we developed the FastPCA software, which employs recent advances in random matrix theory to accurately approximate top PCs while reducing time and memory cost from quadratic to linear in the number of individuals, a computational improvement of many orders of magnitude. We apply FastPCA to a cohort of 54,734 European Americans, identifying 5 distinct subpopulations spanning the top 4 PCs. Using the PC-based test for natural selection, we replicate previously known selected loci and identify three new genome-wide significant signals of selection, including selection in Europeans at ADH1B. The coding variant rs1229984(∗)T has previously been associated to a decreased risk of alcoholism and shown to be under selection in East Asians; we show that i...Continue Reading

  • References83
  • Citations86

Mentioned in this Paper

Genetic Drift
IGH
Computer Software
Genome-Wide Association Study
European American
Genome
IGFBP3 protein, human
Posterior Cerebral Commissure
Extracellular Matrix
Alcoholic Intoxication, Chronic

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