Common biological networks underlie genetic risk for alcoholism in African‐ and European‐American populations
Year: 2013
Type: article
Study design: Observational Study
Abstract: Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome-wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome-wide SNPs collectively account for risk of AD in two US populations, African-Americans (AAs) and European-Americans (EAs). Analyzing GWAS data for two independent case-control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10(-3) and 2.08 × 10(-4) for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF < 0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.
Source: Genes Brain & Behavior
DOI: 10.1111/gbb.12043
Institutions: Texas Biomedical Research Institute, Virginia Commonwealth University, Washington University in St. Louis, RTI International, University of California San Diego, University of Iowa, University of Iowa Hospitals and Clinics, University of Iowa Health Care, Rutgers, The State University of New Jersey, Indiana University Indianapolis, Indiana University School of Medicine, University of Connecticut, UConn Health, State University of New York, SUNY Downstate Health Sciences University, University at Albany, State University of New York
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Funders: Eli Lilly and Company, Lilly Endowment, State University of New York, Washington University in St. Louis, University of Connecticut, Johns Hopkins University, Virginia Commonwealth University, Texas Biomedical Research Institute, National Institutes of Health, SUNY Downstate Medical Center, School of Medicine, Indiana University, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, National Cancer Institute
Awards: G1083756078, G1921953589, G2048638135, G2146332128, G2481876672, Study of Addiction: Genetics and Environment, G3245180032, G363841575, G3799582765, G4503763930, Genome Wide Association Coordinating Center, G4775479183, G5184311545, G5424457750, FAMILY STUDY OF COCAINE DEPENDENCE, G7093047072, G746875028, G7522350138, G7755649354, G8267674335, G858805679, G8924909668, G9000024769, G9000025954, G9000054071, G9000054199, G9000134904, G9000176579
OpenAlex ID: W2124104447