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Genome‐wide survey in African Americans demonstrates potential epistasis of fitness in the human genome
Author(s) -
Wang Heming,
Choi Yoonha,
Tayo Bamidele,
Wang Xuefeng,
Morris Nathan,
Zhang Xiang,
Broeckel Uli,
Hanis Craig,
Kardia Sharon,
Redline Susan,
Cooper Richard S,
Tang Hua,
Zhu Xiaofeng
Publication year - 2017
Publication title -
genetic epidemiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.301
H-Index - 98
eISSN - 1098-2272
pISSN - 0741-0395
DOI - 10.1002/gepi.22026
Subject(s) - epistasis , biology , genetics , evolutionary biology , locus (genetics) , genome , population , population genetics , gene , demography , sociology
The role played by epistasis between alleles at unlinked loci in shaping population fitness has been debated for many years and the existing evidence has been mainly accumulated from model organisms. In model organisms, fitness epistasis can be systematically inferred by detecting nonindependence of genotypic values between loci in a population and confirmed through examining the number of offspring produced in two‐locus genotype groups. No systematic study has been conducted to detect epistasis of fitness in humans owing to experimental constraints. In this study, we developed a novel method to detect fitness epistasis by testing the correlation between local ancestries on different chromosomes in an admixed population. We inferred local ancestry across the genome in 16,252 unrelated African Americans and systematically examined the pairwise correlations between the genomic regions on different chromosomes. Our analysis revealed a pair of genomic regions on chromosomes 4 and 6 that show significant local ancestry correlation ( P ‐value = 4.01 × 10 −8 ) that can be potentially attributed to fitness epistasis. However, we also observed substantial local ancestry correlation that cannot be explained by systemic ancestry inference bias. To our knowledge, this study is the first to systematically examine evidence of fitness epistasis across the human genome.