Interacting effects of CRHR1 gene and stressful life events on drinking initiation and progression among 19-year-olds.

Research in animals and first results in adolescents have indicated that genetic variation in the corticotropin-releasing hormone receptor 1 (CRHR1) is associated with heavy alcohol consumption related to stress. The purpose of this study was to determine whether two haplotype-tagging single nucleotide polymorphisms covering the CRHR1 gene (rs242938, rs1876831) interact with stressful life events affecting age at drinking initiation and alcohol consumption in young adults. Participants were drawn from the Mannheim Study of Children at Risk, an epidemiological cohort study following the outcome of early risk factors. Structured interviews were administered to 270 participants (125 males, 145 females) at 15 yr and 19 yr to assess age at first drinking and, at 19 yr, to assess current drinking and recent stressful life events. Life events during childhood and child psychopathology were measured using standardized parent interviews. Results indicated that, even after control for a range of confounders, higher numbers of stressful life events prior to drinking onset were significantly related to earlier age at first drink only among homozygotes for the C allele of rs1876831. Earlier age at drinking onset was significantly associated with higher consumption levels in 19-yr-olds. Furthermore, homozygotes of the rs1876831 C allele as well as carriers of the rs242938 A allele, when exposed to stress, exhibited significantly higher drinking activity than carriers of other alleles. These findings extend previous reports by demonstrating that the CRHR1 gene and stressful life events interact to predict both drinking initiation in adolescence and progression of heavy alcohol use in young adulthood.