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 × 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.
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Heming
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Yoonha
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Department of Public Health Science, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Bamidele
authors.initials: B
authors.lastname: Tayo
authors.affiliation: Departments of Preventive Medicine, Biomedical Informatics, and Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY, USA.
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Morris
authors.affiliation: Department of Electrical Engineering and Computer Science, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA.
authors.forename: Uli
authors.initials: U
authors.lastname: Broeckel
authors.affiliation: Department of Epidemiology, Human Genetics and Environmental Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Hanis
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Kardia
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: Department of Public Health Science, Loyola University Medical Center, Maywood, IL, USA.
authors.forename: Richard S
authors.initials: RS
authors.lastname: Cooper
authors.affiliation: Department of Genetics, Stanford University, Stanford, CA, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
mesh_terms: D001741:Black or African American / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D004843:Epistasis, Genetic / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics*; D005828:Genetics, Population; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008957:Models, Genetic
chemical_list: D005819:Genetic Markers
keywords: admixed population; coevolution; epistasis of fitness; natural selection