Baik I, Cho NH, Kim SH, Han BG, Shin C. Genome-wide association studies identify genetic loci related to alcohol consumption in Korean men. Am J Clin Nutr 93: 809-816

Department of Foods and Nutrition, College of Natural Sciences, Kookmin University, Seoul, Republic of Korea.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 03/2011; 93(4):809-16. DOI: 10.3945/ajcn.110.001776
Source: PubMed


Genome-wide association (GWA) studies regarding the quantitative trait of alcohol consumption are limited.
The objective of the study was to explore genetic loci associated with the amount of alcohol consumed.
We conducted a GWA study with discovery data on single nucleotide polymorphisms (SNPs) for 1721 Korean male drinkers aged 40-69 y who were included in an urban population-based cohort. Another sample that comprised 1113 male drinkers who were from an independent cohort enrolled in a rural area served as a resource for replication. At baseline (18 June 2001 through 29 January 2003), members of both cohorts provided information on average daily alcohol consumptions, and their DNA samples were collected for genotyping.
We tested 315,914 SNPs of discovery data by using multivariate linear regression analysis adjusted for age and smoking, and 12 SNPs on chromosome 12q24 had genome-wide significant associations with alcohol consumption; adjusted P values by using Bonferroni correction were 1.6 × 10(-5) through 5.8 × 10(-46). We observed most SNPs in intronic regions and showed that the genes that harbor SNPs were C12orf51, CCDC63, MYL2, OAS3, CUX2, and RPH3A. In particular, signals in or near C12orf51, CCDC63, and MYL2 were successfully replicated in the test for 317,951 SNPs; rs2074356 in C12orf51 was in high linkage disequilibrium with SNPs in ALDH2, but other SNPs were not.
In a GWA study, we identified loci and alleles highly associated with alcohol consumption. The findings suggest the need for further investigations on the genetic propensity for drinking excessive amounts of alcohol.

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    • "In addition, we analyzed six published transcriptional profiling data sets performed on different areas of postmortem human brains and also included candidate genes for alcohol-related phenotypes from the HuGE Navigator database (Lewohl et al. 2000; Mayfield et al. 2002; Sokolov et al. 2003; Iwamoto et al. 2004; Flatscher-Bader et al. 2005; Liu et al. 2006a; Guo et al. 2009). Furthermore, we integrated information from GWAS, considering all candidate genes that were nominally significant (Johnson et al. 2006; Liu et al. 2006b; Dick et al. 2008; Treutlein et al. 2009; Bierut et al. 2010; Edenberg et al. 2010; Lind et al. 2010; Baik et al. 2011; Heath et al. 2011; Schumann et al. 2011; Wang et al. 2011a, b; Zuo et al. 2011, 2012, 2013a, b; Kapoor et al. 2013; Pan et al. 2013) and ranked these genes based on how many times within and between species they were replicated (supplementary Table 1). We found only seven genes that were replicated across all four species, ARIH1, COPB2, DLG2, IGF2R, IMPA2, MAX and SHC3, and 139 genes were replicated among any two model organisms and humans, including ALDH1A1, ADD1, APOD, AUTS2, CAT, CAST, CRYAB, GABBR1, NFKB1, NRD1, PDIA3, PRKCA and TACR3 (supplementary Table 1). "
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    ABSTRACT: Alcohol abuse and alcoholism incur a heavy socioeconomic cost in many countries. Both genetic and environmental factors contribute to variation in the inebriating effects of alcohol and alcohol addiction among individuals within and across populations. From a genetics perspective, alcohol sensitivity is a quantitative trait determined by the cumulative effects of multiple segregating genes and their interactions with the environment. This review summarizes insights from model organisms as well as human populations that represent our current understanding of the genetic and genomic underpinnings that govern alcohol metabolism and the sedative and addictive effects of alcohol on the nervous system. Electronic supplementary material The online version of this article (doi:10.1007/s00438-013-0808-y) contains supplementary material, which is available to authorized users.
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    • "Some markers in HTR4 are detected to be associated with AUD, and it is especially noteworthy that the association remained statistically significant after adjustment for multiple tests — not only for the single locus, but also for the haplotype. This finding positively echoes the finding in a GWAS study in a Korean population, which suggested that four interesting genes — the cholinergic receptor/muscarinic 3 (CHRM3) gene; the phosphodiesterase 4D/cyclicAMP-specific (PDE4D) gene; the neuronal periodic acid Schiff (PAS) domain protein 3 (NPAS3) gene; and the HTR4 gene — might be associated with amount of alcohol consumption from additive-model analyses with pooled data [52]. "
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    • "DAD-4926; No. of Pages 7 et al., 2010; Kim et al., 2011; Baik et al., 2011). Based on the current findings it will be interesting to take into account the substantive non-additive genetic variation underlying the association of alcohol intake and GGT by performing gene-finding studies that assume a (2 df) genotypic model instead of an (1 df) additive model. "
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