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Novel QTL at chromosome 6p22 for alcohol consumption: Implications for the genetic liability of alcohol use disorders
Author(s) -
Kos Mark Z.,
Glahn David C.,
Carless Melanie A.,
Olvera Rene,
McKay D. Reese,
Quillen Ellen E.,
Gelernter Joel,
Chen XiangDing,
Deng HongWen,
Kent Jack W.,
Dyer Thomas D.,
Göring Harald H.H.,
Curran Joanne E.,
Duggirala Ravi,
Blangero John,
Almasy Laura
Publication year - 2014
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32231
Subject(s) - quantitative trait locus , genetics , genetic linkage , alcohol dependence , genome wide association study , candidate gene , pedigree chart , chromosome , locus (genetics) , biology , single nucleotide polymorphism , population , gene , medicine , alcohol , genotype , environmental health , biochemistry
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 (h 2 = 0.32 ± 0.05; P = 4.61 × 10 −14 ) with a strong genetic correlation with AUD (ρ g = 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.