title: Exploring the genetic architecture of alcohol dependence in African-Americans via analysis of a genomewide set of common variants.
abstract: Alcohol dependence (AD) is a complex psychiatric disorder that affects about 12.5 % of US adults. Genetic factors play a major role in the development of AD. We conducted a genomewide association study in 2,875 African-Americans including 1,719 AD cases and 1,156 controls. We used the Illumina Omni 1-Quad microarray, which yielded 769,498 single-nucleotide polymorphisms (SNPs) after quality control. To explore the genetic architecture of AD, we estimated the variance that could be explained by all SNPs and subsets of SNPs using two different approaches to genome partitioning. We found that 23.9 % (s.e. 9.3 %) of the phenotypic variance could be explained by using all of the common SNPs on the array. We also found a significant linear relationship between the proportion of the top SNPs used and the phenotypic variance explained by them. Based on genome partitioning of common variants, we also observed a significant linear relationship between the variance explained by a chromosome and its length. Chromosome 4, known to contain several AD risk genes, accounted for excess risk in proportion to its length. By functional partitioning, we found that the genetic variants within 20 kb of genes explained 17.5 % (s.e. 11.4 %) of the phenotypic variance. Our findings are consistent with the generally accepted view that AD is a highly polygenic trait, i.e., the genetic risk in AD appears to be conferred by multiple variants, each of which may have a small or moderate effect.
authors.affiliation: Department of Biostatistics, Yale School of Public Health, Yale University, New Haven, Connecticut, 06520, USA, can.yang@yale.edu.
authors.forename: Can
authors.initials: C
authors.lastname: Yang
authors.forename: Cong
authors.initials: C
authors.lastname: Li
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000437:Alcoholism / Q000208:ethnology / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D001741:Black or African American