Genome‐wide survey in African Americans demonstrates potential epistasis of fitness in the human genome
Year: 2016
Type: article
Study design: Observational Study
Abstract: 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.
Source: Genetic Epidemiology
DOI: 10.1002/gepi.22026
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Awards: CARDIA, G105512408, HYPERGEN, G1220223050, CORONARY HEART DISEASE AND STROKE, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G1325221871, G1409423729, CHS-ULTRASOUND READING, CARDIA, G1612023617, CORONARY HEART DISEASE AND STROKE, G1639455850, G1658243001, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, CARDIA, G176868078, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G2076123899, G2081319657, Atherosclerosis Risk in Communities Study (ARIC), CARDIA-ECHOCARDIOGRAPHY READING, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, G2391884931, CARDIA, CCSP FIELD CENTER, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, G2786045897, G2856445237, SUBCLINICAL CARDIOVASCULAR DISEASE STUDY--EBCT READING, G3045517347, LONGITUDINAL STUDIES OF CORONARY HEART DISEASE RISK FACTORS IN YOUNG ADULTS, G3107571658, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3236609591, G328935669, Familial Aggregation and Natural History of Sleep Apnea, G3396487927, G3444966432, G3555325704, G3647016462, Statistical methods for analyzing high-throughput genotype and sequencing data, CANDIDATE GENE ASSOCIATION RESOURCE (CARE), G390162502, G3912115555, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Genetic Mechanisms of Arteriosclerosis in Hypertensive Sibships, G4048755144, G4165892905, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G4458374387, Atherosclerosis Risk in Communities Study (ARIC), G4617276643, G4802923568, G483429595, CARDIA, G50331642, G50822097, G5418383269, G5452216648, Atherosclerosis Risk in Communities Study (ARIC), G581887176, G5850384408, G587882820, Genetics of Hypertension in Blacks, CHS Events Follow-up Study, G6203107232, G6226795708, HYPERGEN CENTRAL BIOCHEMISTRY LABORATORY, Genetics of Hypertension Risk Factors and Sequela in African Americans, G6520056932, CHS-Transition Phase, G6755603029, G7176672723, MESA, G7518182772, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G7999488110, G812579647, G8173324991, G8402048158, G8486527673, G8593276544, HyperGEN: Genetics of Left Ventricular Hypertrophy, G8658148070, G878552033, G9000072420, Moffitt Cancer Center Support Grant, G918291509, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2560001398