|The Effects of Migration and Assortative Mating on Admixture Linkage Disequilibrium.
|Year of Publication
|Zaitlen, N, Huntsman, S, Hu, D, Spear, M, Eng, C, Oh, SS, White, MJ, Mak, A, Davis, A, Meade, K, Brigino-Buenaventura, E, LeNoir, MA, Bibbins-Domingo, K, Burchard, EG, Halperin, E
|Alleles, Black or African American, Datasets as Topic, Gene Frequency, Genetics, Population, Genomics, Human Migration, Humans, Linkage Disequilibrium, Models, Genetic, Models, Statistical, Polymorphism, Single Nucleotide
Statistical models in medical and population genetics typically assume that individuals assort randomly in a population. While this simplifies model complexity, it contradicts an increasing body of evidence of nonrandom mating in human populations. Specifically, it has been shown that assortative mating is significantly affected by genomic ancestry. In this work, we examine the effects of ancestry-assortative mating on the linkage disequilibrium between local ancestry tracks of individuals in an admixed population. To accomplish this, we develop an extension to the Wright-Fisher model that allows for ancestry-based assortative mating. We show that ancestry-assortment perturbs the distribution of local ancestry linkage disequilibrium (LAD) and the variance of ancestry in a population as a function of the number of generations since admixture. This assortment effect can induce errors in demographic inference of admixed populations when methods assume random mating. We derive closed form formulae for LAD under an assortative-mating model with and without migration. We observe that LAD depends on the correlation of global ancestry of couples in each generation, the migration rate of each of the ancestral populations, the initial proportions of ancestral populations, and the number of generations since admixture. We also present the first direct evidence of ancestry-assortment in African Americans and examine LAD in simulated and real admixed population data of African Americans. We find that demographic inference under the assumption of random mating significantly underestimates the number of generations since admixture, and that accounting for assortative mating using the patterns of LAD results in estimates that more closely agrees with the historical narrative.
|PubMed Central ID
|R01 ES015794 / ES / NIEHS NIH HHS / United States
K12 GM081266 / GM / NIGMS NIH HHS / United States
U01 HG009080 / HG / NHGRI NIH HHS / United States
R01 HL117004 / HL / NHLBI NIH HHS / United States
P60 MD006902 / MD / NIMHD NIH HHS / United States
R21 ES024844 / ES / NIEHS NIH HHS / United States
K25 HL121295 / HL / NHLBI NIH HHS / United States
R01 MD010443 / MD / NIMHD NIH HHS / United States