The maximum number of drinks an individual has ever consumed in a 24-hour period(maxdrinks) is highly correlated with risk for alcohol dependence and has been utilized inprevious genetic studies, including successful gene localizations via linkage analysis. The goalof this study was to conduct genome-wide association analyses to localize genes influencingvariation in maxdrinks. Maxdrinks was assessed in 1195 Mexican American participants inextended pedigrees from the San Antonio Family Study, along with lifetime history of alcoholabuse or dependence derived from the MINI-Plus psychiatric screening questionnaire. Thesample was 63% female and ranged in age from 26 – 85 years (mean 48.4). Reportedmaxdrinks ranged from 0 – 216, and 34.4% of individuals met criteria for lifetime history ofalcohol abuse or dependence. Participants were genotyped for approximately one millionSNPs on Illumina microarrays. After removal of monoallelic SNPs and SNPs with low callrates, 931,219 markers remained. Genome-wide association analyses were conducted usingan additive measured genotype model, correcting for the non-independence among familymembers. Bivariate genetic analyses confirmed a strong correlation between maxdrinks andlifetime history of alcohol abuse or dependence and supported both shared genetic influences(qg=0.98; p=1.4x10-10) and shared environmental influences (qe=0.48; p=3.1x10-9). Genome-wide association identified one significant signal for maxdrinks on chromosome 8 atrs17293712 (v2=29.5, p= 5.0x10-8, MAF=0.096), which also showed nominal evidence ofassociation with lifetime history of alcohol abuse (p=0.018). This SNP is located in the intronof the cytochrome P450, family 7, subfamily B, polypeptide 1 (CYP7B1) gene, which encodesa member of the cytochrome P450 superfamily. The cytochrome P450 proteins aremonooxygenases that catalyze reactions involved in drug metabolism and synthesis ofcholesterol, steroids and other lipids. Although CYP7B1 has not previously been associatedwith alcoholism, it is highly expressed in human hippocampus, a brain region altered inindividuals at risk for alcoholism. In addition, a closely related gene, CYP2E1, has beenimplicated in alcohol dependence in previous studies. We are currently sequencing individualsin a subset of these families to identify putative functional variants in and around CYP7B1
|Publication status||Published - 2012|
|Event||35th Annual Scientific Meeting of the Research Society on Alcoholism - Sa Francisco, United States|
Duration: 23 Jun 2012 → 27 Jun 2012
|Conference||35th Annual Scientific Meeting of the Research Society on Alcoholism|
|Period||23/06/12 → 27/06/12|
Almasy, L., Carless, M. A., Olvera, R. L., Kent, J., Dyer, T. D., Johnson, M. P., Curran, J. E., Moses, E. K., Goering, H. H., Duggirala, R., Blangero, J., & Glahn, D. C. (2012). Genome-wide association of maxdrinks implicates a novel risk locus for alcohol dependence: CYP7B1. 319A-319A. Abstract from 35th Annual Scientific Meeting of the Research Society on Alcoholism, Sa Francisco, United States.