A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks.
paper
Primary
Public
- Authors
- Kapoor, Manav; Wang, Jen-Chyong; Wetherill, Leah; Le, Nhung; Bertelsen, Sarah; Hinrichs, Anthony L; Budde, John; Agrawal, Arpana; Bucholz, Kathleen; Dick, Danielle; Harari, Oscar; Hesselbrock, Victor; Kramer, John; Nurnberger, John I; Rice, John; Saccone, Nancy; Schuckit, Marc; Tischfield, Jay; Porjesz, Bernice; Edenberg, Howard J; Bierut, Laura; Foroud, Tatiana; Goate, Alison
- Year
- 2013
- Journal
- Human genetics
- PMID
- 23743675
- DOI
- 10.1007/s00439-013-1318-z
- PMCID
- PMC3776011
Maximum number of alcoholic drinks consumed in a 24-h period (maxdrinks) is a heritable (>50 %) trait and is strongly correlated with vulnerability to excessive alcohol consumption and subsequent alcohol dependence (AD). Several genome-wide association studies (GWAS) have studied alcohol dependence, but few have concentrated on excessive alcohol consumption. We performed two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from the Collaborative Study on the Genetics of Alcoholism (COGA), and the other in a case-control sample (N = 2,593) derived from the Study of Addiction: Genes and Environment (SAGE). The strongest association in the COGA families was detected with rs9523562 (p = 2.1 × 10(-6)) located in an intergenic region on chromosome 13q31.1; the strongest association in the SAGE dataset was with rs67666182 (p = 7.1 × 10(-7)), located in an intergenic region on chromosome 8. We also performed a meta-analysis with these two GWAS and demonstrated evidence of association in both datasets for the LMO1 (p = 7.2 × 10(-7)) and PLCL1 genes (p = 4.1 × 10(-6)) with maxdrinks. A variant in AUTS2 and variants in INADL, C15orf32 and HIP1 that were associated with measures of alcohol consumption in a meta-analysis of GWAS studies and a GWAS of alcohol consumption factor score also showed nominal association in the current meta-analysis. The present study has identified several loci that warrant further examination in independent samples. Among the top SNPs in each of the dataset (p ≤ 10(-4)) far more showed the same direction of effect in the other dataset than would be expected by chance (p = 2 × 10(-3), 3 × 10(-6)), suggesting that there are true signals among these top SNPs, even though no SNP reached genome-wide levels of significance.
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| Name | Type |
|---|---|
| 1000 Genomes Project | cohort |
| A2BP1 | gene |
| ADH1B | gene |
| African American | cohort |
| African-Americans | cohort |
| age | phenotype |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| Alcohol Dependence Symptoms | phenotype |
| alcoholic liver disease | phenotype |
| alcoholism | phenotype |
| alcohol preference | phenotype |
| Asian | cohort |
| AUTS2 | gene |
| AUTS2 SNP local | variant |
| Beagle | drug |
| beta subunits of GABA(A) receptors local | drug |
| birth cohort | cohort |
| brain | anatomy |
| breast cancer | phenotype |
| C15orf32 local | gene |
| CACNG2 | gene |
| cancer | phenotype |
| cardiovascular disease | phenotype |
| Center for Inherited Diseases Research local | cohort |
| Chromosome 12 SNPs local | variant |
| chronic pancreatitis local | phenotype |
| cocaine | phenotype |
| COGA dataset | cohort |
| COGA sample | cohort |
| COGEND | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| CYP4F8 local | gene |
| dLmo local | gene |
| EA sample | cohort |
| EIGENSTRAT | drug |
| ethanol consumption | phenotype |
| ethanol-induced sedation local | phenotype |
| EUR analysis panel local | cohort |
| European ancestry | cohort |
| European descent families local | cohort |
| European population | cohort |
| excessive alcohol consumption | phenotype |
| EXOC5 local | gene |
| FABP5 local | gene |
| FARS2 local | gene |
| FSCD | cohort |
| GABA(A) receptor associated protein local | drug |
| Geneva | cohort |
| HapMap | cohort |
| HapMap European reference samples local | cohort |
| HIP1 local | gene |
| Illumina 1M chip local | drug |
| Illumina Human 1 M beadchip local | drug |
| Illumina Human OmniExpress array 12.VI local | drug |
| Illumina Omni Express local | drug |
| INADL | gene |
| Johns Hopkins University | cohort |
| Korean men | cohort |
| LincRNA 13q31.1 local | gene |
| LMO1 | gene |
| Lmo3 | gene |
| Lmo3−/− mice local | cohort |
| malabsorption local | phenotype |
| maxdrinks | phenotype |
| metal | drug |
| MGS control sample local | cohort |
| MKLN1 local | gene |
| MPHOSPH6 local | gene |
| Ncam2 | gene |
| nicotine dependence | phenotype |
| PLCL1 | gene |
| rare and novel variants local | variant |
| rare highly penetrant variants local | variant |
| rs10180112 local | variant |
| rs1064213 local | variant |
| rs110419 local | variant |
| rs1229984 | variant |
| rs1579695 local | variant |
| rs2283970 local | variant |
| rs4758317 local | variant |
| rs67031482 local | variant |
| rs67666182 local | variant |
| rs9523562 local | variant |
| SAGE | cohort |
| SAGE dataset | cohort |
| SAGE EA | cohort |
| SAGE GWAS | cohort |
| sex | phenotype |
| SH3GL3 local | gene |
| shLmo3.8 local | drug |
| shScr local | drug |
| SLC26A4 local | gene |
| SNP | cohort |
| SNX16 local | gene |
| TLR1 local | gene |
| TLR10 local | gene |
| trait | phenotype |
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