Genome-wide survey in African Americans demonstrates potential epistasis of fitness in the human genome. Genet Epidemiol 2017 Feb;41(2):122-135
Date
12/06/2016Pubmed ID
27917522Pubmed Central ID
PMC5226866DOI
10.1002/gepi.22026Scopus ID
2-s2.0-85008253490 (requires institutional sign-in at Scopus site) 8 CitationsAbstract
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.
Author List
Wang H, Choi Y, Tayo B, Wang X, Morris N, Zhang X, Broeckel U, Hanis C, Kardia S, Redline S, Cooper RS, Tang H, Zhu XAuthor
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cardiovascular DiseasesCohort Studies
Epistasis, Genetic
Genetic Markers
Genetics, Population
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Models, Genetic
