Genomewide Association Study for Maximum Number of Alcoholic Drinks in European Americans and African Americans.
- Authors
- Xu, Ke; Kranzler, Henry R; Sherva, Richard; Sartor, Carolyn E; Almasy, Laura; Koesterer, Ryan; Zhao, Hongyu; Farrer, Lindsay A; Gelernter, Joel
- Year
- 2015
- Journal
- Alcoholism, clinical and experimental research
- PMID
- 26036284
- DOI
- 10.1111/acer.12751
- PMCID
- PMC4706077
BACKGROUND: We conducted a genomewide association study (GWAS) for maximum number of alcoholic drinks consumed in a 24-hour period ("MaxDrinks"), in 2 independent samples comprised of over 9,500 subjects, following up on our GWAS for alcohol dependence (AD) in European Americans (EAs) and African Americans (AAs). METHODS: The samples included our GWAS samples (Yale-UPenn) recruited for studies of the genetics of drug or AD, and a publicly available sample: the Study of Addiction: Genetics and Environment (SAGE). Genomewide association analysis was performed for ~890,000 single nucleotide polymorphisms (SNPs) using linear association random effects models. EAs and AAs were separately analyzed. RESULTS: The results confirmed significant associations of the well-known functional loci at ADH1B with MaxDrinks in EAs (rs1229984 Arg48His p = 5.96 × 10(-15) ) and AAs (rs2066702 Arg370Cys, p = 2.50 × 10(-10) ). The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs. We also identified potentially novel significant common SNPs for MaxDrinks in EAs in the Yale-UPenn sample: rs1799876 at SERPINC1 on chromosome 1 (4.00 × 10(-8) ) and rs2309169 close to ANKRD36 on chromosome 2 (p = 5.58 × 10(-9) ). After adjusting for the peak SNP rs1229984 on ADH1B, rs1799876 was nearly significant (p = 1.99 × 10(-7) ) and rs2309169 remained highly significant (2.12 × 10(-9) ). CONCLUSIONS: The results provide further support that ADH1B modulates alcohol consumption. Future replications of potential novel loci are warranted. This is the largest MaxDrinks GWAS to date, the first in AAs.
Manhattan plot and QQ plot in European Americans (EA) in the Yale-UPenn sample. The peak SNP was rs1229984 (ADH1B) on chromosome 4 (p=5.96 x 10-15). Two novel loci were rs1799876 on chromosome 1 (p=4.00 x 10-8) and rs2309169 on chromosome 2 (5.58 x 10-9). After adjusting for rs122984 on ADH1B, rs2309169 remained significant (p=2.1 x 10-9), but rs1799876 was nearly significant (p=1.99 x 10-7).
Manhattan plot and QQ plot in African Americans (AAs) in the combination of the Yale-UPenn samples and the SAGE samples. Eight SNPs on chromosome 4 reached genome-wide significance. The peak SNP was rs2066702 (ADH1B) on chromosome 4 (p=2.50 x 10-10).
Chromosome 4 regional Manhattan plots in the combination of the Yale-UPenn samples and the SAGE samples. Left: European Americans: The peak significant SNP was rs1229984 on ADH1B (p=5.96 x 10-15) Right: African Americans: The peak significant SNP was rs2066702 on ADH1B (p=2.50 x 10-10)
The distribution of number of maximal drinks within 24 hours by two-peak significant SNPs. Left: rs1229984 in European Americans; Right rs2066702 in African Americans. The number of drinks was binned by five drinks. The number of drinks greater than 45 was combined into one group.
| Name | Type |
|---|---|
| 1000 Genomes dataset local | cohort |
| AA | cohort |
| AA population | cohort |
| AA sample | cohort |
| acetaldehyde | drug |
| ADH1B | gene |
| ADH1C | gene |
| AD symptom count | phenotype |
| African American | cohort |
| African American (AA) samples local | cohort |
| African descent individuals local | cohort |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcohol-related phenotypes | phenotype |
| ALDH2 | gene |
| Alzheimer's disease | phenotype |
| ANKRD36 local | gene |
| Asian | cohort |
| Australian local | cohort |
| Australian twin population local | cohort |
| Australian Twin Registry | cohort |
| body mass index | phenotype |
| C12orf51 | gene |
| CCDC88A | gene |
| Chinese population | cohort |
| cocaine | phenotype |
| COGEND | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| Combined Yale-Upenn and SAGE local | cohort |
| DDC | gene |
| drug dependence | phenotype |
| DSM criterion count local | phenotype |
| EA | cohort |
| EA population | cohort |
| EAs | cohort |
| European American (EA) samples local | cohort |
| European ancestry | cohort |
| European population | cohort |
| Fagerström Test for Nicotine Dependence | phenotype |
| flushing response to alcohol local | phenotype |
| FSCD | cohort |
| Gene Environment Association Studies | cohort |
| Heaviness of alcohol drinking factor score local | phenotype |
| Impute2 | drug |
| Irish affected sibpairs local | cohort |
| Israeli local | cohort |
| Kcnb2 | gene |
| Korean men | cohort |
| LMO1 | gene |
| LOC100507053 | gene |
| LogM local | phenotype |
| maxdrinks | phenotype |
| metal | drug |
| METAP local | gene |
| MTIF2 local | gene |
| nicotine | drug |
| nicotine dependence | phenotype |
| opioid | drug |
| opioid dependence | phenotype |
| past-year drinking | phenotype |
| PDL1M5 local | gene |
| PLCL1 | gene |
| rs1040883 local | variant |
| rs1128951 local | variant |
| rs1229984 | variant |
| rs1693457 | variant |
| rs1789882 local | variant |
| rs1799865 local | variant |
| rs1799876 | variant |
| rs200475889 | variant |
| rs20047889 local | variant |
| rs2066207 local | variant |
| rs2066702 | variant |
| rs2309169 | variant |
| rs34009511 local | variant |
| rs671 | variant |
| rs9512637 | variant |
| SAGE | cohort |
| SAGE cohort local | cohort |
| SAGE dataset | cohort |
| SAGE samples local | cohort |
| SERPINC1 | gene |
| Smpd1 | gene |
| SNP (chr4 region) local | variant |
| SNPs (genome-wide) local | variant |
| Study of Addiction: Genetics and Environment | cohort |
| substance dependence comorbidity local | phenotype |
| thrombosis-related phenotypes local | phenotype |
| Yale-Upenn local | cohort |
| Yale-UPenn local | cohort |
| Yale-UPenn and SAGE samples local | cohort |
| Yale-UPenn cohort local | cohort |
| Yale-Upenn EA sample local | cohort |
| Yale-UPenn sample local | cohort |
| Yale-UPenn samples local | cohort |
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