Year: 2023
Type: preprint
Abstract: Recent positive selection can result in an excess of long identity-by-descent (IBD) haplotype segments. The statistical methods that we propose here address three major objectives in studying classical selective sweeps: scanning for regions of interest, identifying possible sweeping alleles, and estimating a selection coefficient s . First, we implement a selection scan to locate regions of excess IBD rate. Second, we develop a statistic to rank alleles in strong linkage disequilibrium with a putative sweeping allele. We aggregate these scores to estimate the allele frequency of the sweeping allele, even if it is not genotyped. Lastly, we propose an estimator for the selection coefficient and quantify uncertainty using the parametric bootstrap. Comparing against state-of-the-art methods in extensive simulations, we show that our methods are better at pinpointing alleles at low frequency and estimating s ≥ 0.015. We apply these methods to study positive selection in inferred European ancestry samples from the TOPMed project. We find twelve loci where their IBD rates exceed four standard deviations above the population median. The excess IBD rate at LCT is thirty-five standard deviations above the population median, and our estimates of its selection coefficient imply strong selection within the past 120 to 163 generations. Overall, we present robust and accurate new approaches to study very recent adaptive evolution under mild assumptions.
Authors: Seth D. Temple, Ryan K. Waples, Sharon R. Browning, Sharon R. Browning
Institution: University of Washington
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: American Heart Association, Andrea and Charles Bronfman Philanthropies, Vanderbilt University, Jackson State University, Cleveland Clinic, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Defense Science and Engineering Graduate, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of General Medical Sciences, National Center for Research Resources, National Center for Advancing Translational Sciences, National Institute on Minority Health and Health Disparities
Awards: G1052645489, G105512408, G112182703, G115643725, G1213528134, G1216488641, G1234334611, G1303440240, G1314613728, G143060900, Pharmacogenomics of Arrhythmia Therapy, G1474727569, G1531600799, G1609525565, G1735617348, G185044200, G1885842644, G2008013691, G2043477120, G2081319657, G2096685756, G2187730879, G2208403735, G2223174309, Case Western Reserve University/Cleveland Clinic CTSA (UL1), G232264632, G2513218708, G2553331515, G264675175, G272281204, G278200998, G2901416272, G3001391456, G3031759, G3047562346, G3078883119, G3272238124, G3395363768, IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVAL, G361393594, G364208108, G3724712001, G3860363877, G3981545571, G4030405119, Diverse ancestry biobank to map biomedical traits and elucidate health disparitie, G4175770015, G4423964575, G4464225719, G4608159596, G475755283, G483429595, G4976486911, G50080621, G5346183306, Predoctoral Research Training in Statistical Genetics, G560889077, G56766395, G5679716143, G5805320778, G6089578186, The Vanderbilt Institute for Clinical and Translational Research (VICTR) UL1, G631129105, G6615318374, G670838961, G6717867015, Positional Cloning and Candidate Gene Approach to Familial Atrial Fibrilation, G6822215221, G701224828, G7226679574, G7290764386, G743178690, G746714636, G7518182772, G7604803519, The Vanderbilt Institute for Clinical and Translational Research (VICTR), G794672604, G829395128, Studies of Rare Genetic Variation in the Isolated Population of Sardinia, HyperGEN: Genetics of Left Ventricular Hypertrophy, G8683204365, G8837687070, G8993135685, G9000015671, G9000018693, G9000022338, G9000029256, G9000032027, G9000043901, G9000053952, G9000058341, G9000059356, G9000085589, G9000135092, G9000156732, G9000171545, G9000237806, G9000281696, G9000283691, G9000291397, G9000300101
OpenAlex ID: W4388744730