title: Test for association of common variants in GRM7 with alcohol consumption.
abstract: Recent work using a mouse model has identified the glutamate metabotropic receptor 7 (Grm7) gene as a strong candidate gene for alcohol consumption. Although there has been some work examining the effect of human glutamate metabotropic receptor 7 (GRM7) polymorphisms on human substance use disorders, the majority of the work has focused on other psychiatric disorders such as ADHD, major depressive disorder, schizophrenia, bipolar disorder, panic disorder, and autism spectrum disorders. The current study aimed to evaluate evidence for association between GRM7 and alcohol behaviors in humans using a single nucleotide polymorphism (SNP) approach, as well as a gene-based approach. Using 1803 non-Hispanic European Americans (EAs) (source: the Colorado Center on Antisocial Drug Dependence [CADD]) and 1049 EA subjects from an independent replication sample (source: the Genetics of Antisocial Drug Dependence [GADD]), two SNPs in GRM7 were examined for possible association with alcohol consumption using two family-based association tests implemented in FBAT and QTDT. Rs3749380 was suggestively associated with alcohol consumption in the CADD sample (p = 0.010) with the minor T allele conferring risk. There was no evidence for association in the GADD sample. A gene-based test using four Genome-Wide Association Studies (GWAS) revealed no association between variation in GRM7 and alcohol consumption. This study had several limitations: the SNPs chosen likely do not tag expression quantitative trait loci; a human alcohol consumption phenotype was used, complicating the interpretation with respect to rodent studies that found evidence for a cis-regulatory link between alcohol preference and Grm7; and only common SNPs imputed in all four datasets were included in the gene-based test. These limitations highlight the fact that rare variants, some potentially important common signals in the gene, and regions farther upstream were not examined.
authors: Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: Whitney E
authors: WE
authors: Melroy-Greif
authors: Nathan Kline Institute for Psychiatric Research, New York University School of Medicine, Orangeburg, NY 10962, USA.
authors: Csaba
authors: C
authors: Vadasz
authors: Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA 16802, USA.
authors: Helen M
authors: HM
authors: Kamens
authors: Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA.
authors: Matthew B
authors: MB
authors: McQueen
authors: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: Robin P
authors: RP
authors: Corley
authors: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: Michael C
authors: MC
authors: Stallings
authors: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: Christian J
authors: CJ
authors: Hopfer
authors: Department of Molecular and Cellular Biology, University of Colorado, Boulder, CO 80309, USA.
authors: Kenneth S
authors: KS
authors: Krauter
authors: Department of Psychology and Psychiatry, University of California, San Diego, CA 92093, USA.
authors: Sandra A
authors: SA
authors: Brown
authors: Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA.
authors: John K
authors: JK
authors: Hewitt
authors: Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA; Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA. Electronic address: Marissa.Ehringer@colorado.edu.
authors: Marissa A
authors: MA
authors: Ehringer
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D055815:Young Adult
chemical_list: D018094:Receptors, Metabotropic Glutamate; C102719:metabotropic glutamate receptor 7
keywords: Alcohol consumption; Family-based test; Gene test; Glutamate metabotropic receptor 7; Human genetics