Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome Journal Article

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Authors: Wang, H; Choi, Y.; Tayo, B; Wang, X; Morris, N; Zhang, X; Broeckel, U; Hanis, C.; Kardia, S.; Redline, S; Cooper, R. S.; Tang, H; Zhu, X
Article Title: Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome
Abstract: 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 x 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.
Journal Title: Genetic epidemiology
Volume: 41
Issue: 2
ISSN: 1098-2272; 0741-0395
Publisher: Wiley Periodicals, Inc  
Journal Place: United States
Date Published: 2017
Start Page: 122
End Page: 135
Language: eng
DOI/URL:

10.1002/gepi.22026
Notes: LR: 20170220; CI: (c) 2016; GR: N01HC55020/HL/NHLBI NIH HHS/United States; GR: U10 HL054472/HL/NHLBI NIH HHS/United States; GR: U01 HL054472/HL/NHLBI NIH HHS/United States; GR: R01 HL053353/HL/NHLBI NIH HHS/United States; GR: U01 HL054471/HL/NHLBI NIH HHS/United States; GR: U01 HL054496/HL/NHLBI NIH HHS/United States; GR: U10 HL054497/HL/NHLBI NIH HHS/United States; GR: R01 HG003054/HG/NHGRI NIH HHS/United States; GR: N01HC55018/HL/NHLBI NIH HHS/United States; GR: R01 HL046380/HL/NHLBI NIH HHS/United States; GR: U10 HL054509/HL/NHLBI NIH HHS/United States; GR: U01 HL080295/HL/NHLBI NIH HHS/United States; GR: N01HC48049/HL/NHLBI NIH HHS/United States; GR: N01HC45205/HL/NHLBI NIH HHS/United States; GR: R01 HL087660/HL/NHLBI NIH HHS/United States; GR: U01 HL054497/HL/NHLBI NIH HHS/United States; GR: N01 HC015103/HC/NHLBI NIH HHS/United States; GR: U01 HL054509/HL/NHLBI NIH HHS/United States; GR: N01HC95169/HL/NHLBI NIH HHS/United States; GR: UL1 RR024156/RR/NCRR NIH HHS/United States; GR: N01 HC085085/HC/NHLBI NIH HHS/United States; GR: N01HC55222/HL/NHLBI NIH HHS/United States; GR: N01HC55015/HL/NHLBI NIH HHS/United States; GR: N01HC85086/HL/NHLBI NIH HHS/United States; GR: N01HC95095/HL/NHLBI NIH HHS/United States; GR: RC1 HL100245/HL/NHLBI NIH HHS/United States; GR: N01HC95159/HL/NHLBI NIH HHS/United States; GR: N01 HC045134/HC/NHLBI NIH HHS/United States; GR: N01HC55016/HL/NHLBI NIH HHS/United States; GR: N01HC65226/HL/NHLBI NIH HHS/United States; GR: N01 HC085084/HC/NHLBI NIH HHS/United States; GR: N01HC48050/HL/NHLBI NIH HHS/United States; GR: N01HC55019/HL/NHLBI NIH HHS/United States; GR: N01HC85082/HL/NHLBI NIH HHS/United States; GR: N01HC75150/HL/NHLBI NIH HHS/United States; GR: N01HC05187/HL/NHLBI NIH HHS/United States; GR: R01 HL086718/HL/NHLBI NIH HHS/United States; GR: N01HC48047/HL/NHLBI NIH HHS/United States; GR: N01HC85083/HL/NHLBI NIH HHS/United States; GR: U10 HL054473/HL/NHLBI NIH HHS/United States; GR: N01HC45204/HL/NHLBI NIH HHS/United States; GR: U10 HL054495/HL/NHLBI NIH HHS/United States; GR: U10 HL054496/HL/NHLBI NIH HHS/United States; GR: U10 HL054471/HL/NHLBI NIH HHS/United States; GR: N01HC85079/HL/NHLBI NIH HHS/United States; GR: N01HC55021/HL/NHLBI NIH HHS/United States; GR: N01 HC045133/HC/NHLBI NIH HHS/United States; GR: N01HC85080/HL/NHLBI NIH HHS/United States; GR: U01 HL054495/HL/NHLBI NIH HHS/United States; GR: N01 HC035129/HC/NHLBI NIH HHS/United States; GR: N01WH22110/WH/WHI NIH HHS/United States; GR: R01 HL055673/HL/NHLBI NIH HHS/United States; GR: U01 HL054473/HL/NHLBI NIH HHS/United States; GR: N01HC48048/HL/NHLBI NIH HHS/United States; GR: N01HC85081/HL/NHLBI NIH HHS/United States; JID: 8411723; NIHMS825005; OTO: NOTNLM; PMCR: 2018/02/01; 2016/08/03 [received]; 2016/09/30 [revised]; 2016/10/03 [accepted]; ppublish