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

Heming Wang, Yoonha Choi, Bamidele Tayo, Xuefeng Wang, Nathan Morris, Xiang Zhang, Uli Broeckel, Craig Hanis, Sharon Kardia, Susan Redline, Richard S. Cooper, Hua Tang, Xiaofeng Zhu

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5 Scopus citations

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 × 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.

Original languageEnglish (US)
Pages (from-to)122-135
Number of pages14
JournalGenetic Epidemiology
Volume41
Issue number2
DOIs
StatePublished - Feb 1 2017

All Science Journal Classification (ASJC) codes

  • Epidemiology
  • Genetics(clinical)

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    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. (2017). Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome. Genetic Epidemiology, 41(2), 122-135. https://doi.org/10.1002/gepi.22026