RT Journal Article SR Electronic T1 Fast principal components analysis reveals independent evolution of ADH1B gene in Europe and East Asia JF bioRxiv FD Cold Spring Harbor Laboratory SP 018143 DO 10.1101/018143 A1 Kevin J. Galinsky A1 Gaurav Bhatia A1 Po-Ru Loh A1 Stoyan Georgiev A1 Sayan Mukherjee A1 Nick J. Patterson A1 Alkes L. Price YR 2015 UL http://biorxiv.org/content/early/2015/08/24/018143.abstract AB 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 data sets, 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 the ADH1B gene. The derived allele of the coding variant rs1229984 has previously been associated to a decreased risk of alcoholism and shown to be under selection in East Asians; we show that it is a rare example of independent evolution on two continents. We also detect new selection signals at IGFBP3 and IGH, which have also previously been associated to human disease.