Novel QTL at chromosome 6p22 for alcohol consumption: Implications for the genetic liability of alcohol use disorders
Article first published online: 1 APR 2014
© 2014 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 165, Issue 4, pages 294–302, June 2014
How to Cite
2014. Novel QTL at Chromosome 6p22 for Alcohol Consumption: Implications for the Genetic Liability of Alcohol Use Disorders. Am J Med Genet Part B 165B:294–302., , , , , , , , , , , , , , , .
- Issue published online: 1 JUN 2014
- Article first published online: 1 APR 2014
- Manuscript Accepted: 10 MAR 2014
- Manuscript Received: 18 SEP 2013
- National Institute of Mental Health Grants. Grant Numbers: MH0708143, MH078111, MH083824
- NIAAA Grants. Grant Numbers: AA015973, AA11330
- National Institute of Mental Health Grant. Grant Number: MH59490
- National Center for Research Resources, National Institutes of Health. Grant Numbers: C06 RR13556, C06 RR017515
- AT&T Foundation
- National Center for Research Resources. Grant Number: S10 RR029392
- alcohol dependence;
- variance components linkage analysis;
- endophenotype ranking value (ERV);
- SNP association
Linkage studies of alcoholism have implicated several chromosome regions, leading to the successful identification of susceptibility genes, including ADH4 and GABRA2 on chromosome 4. Quantitative endophenotypes that are potentially closer to gene action than clinical endpoints offer a means of obtaining more refined linkage signals of genes that predispose alcohol use disorders (AUD). In this study we examine a self-reported measure of the maximum number of drinks consumed in a 24-hr period (abbreviated Max Drinks), a significantly heritable phenotype (h2 = 0.32 ± 0.05; P = 4.61 × 10−14) with a strong genetic correlation with AUD (ρg = 0.99 ± 0.13) for the San Antonio Family Study (n = 1,203). Genome-wide SNPs were analyzed using variance components linkage methods in the program SOLAR, revealing a novel, genome-wide significant QTL (LOD = 4.17; P = 5.85 × 10−6) for Max Drinks at chromosome 6p22.3, a region with a number of compelling candidate genes implicated in neuronal function and psychiatric illness. Joint analysis of Max Drinks and AUD status shows that the QTL has a significant non-zero effect on diagnosis (P = 4.04 × 10−3), accounting for 8.6% of the total variation. Significant SNP associations for Max Drinks were also identified at the linkage region, including one, rs7761213 (P = 2.14 × 10−4), obtained for an independent sample of Chinese families. Thus, our study identifies a potential risk locus for AUD at 6p22.3, with significant pleiotropic effects on the heaviness of alcohol consumption that may not be population specific. © 2014 Wiley Periodicals, Inc.