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Table 1 Previous studies about genome- or phenome-wide association studies of alcohol dependence

From: Lack of associations of the opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with alcohol dependence: review and meta-analysis of retrospective controlled studies

Association type

Author

Year

Country

PMID

Subjects number

Key findings

Genome-wide association studies

Gelernter J et al. [7]

2014

USA

24,166,409

16,087

1. They confirmed well-known risk loci mapped to alcohol-metabolizing enzyme genes, notably ADH1B in European-American (EA) and African-American (AA) populations and ADH1C in AAs, and identified novel risk loci mapping to the ADH gene cluster on chromosome 4 and extending centromerically beyond it to include GWS associations at LOC100507053 in AAs, PDLIM5 in EAs, and METAP in AAs.

2. They also identified a novel GWS association mapped to chromosome 2 at rs1437396, between MTIF2 and CCDC88A, across all of the EA and AA cohorts, with supportive gene expression evidence, and population-specific GWS for markers on chromosomes 5, 9 and 19.

Xu K et al. [8]

2015

USA

26,036,284

9500

1. The results confirmed significant associations of the well-known functional loci at ADH1B with MaxDrinks in EAs and AAs. The region of significant association on chromosome 4 was extended to LOC100507053 in AAs but not EAs.

2. They also identified potentially novel significant common SNPs for MaxDrinks in EAs: rs1799876 at SERPINC1 on chromosome 1 and rs2309169 close to ANKRD36 on chromosome 2.

Mbarek H et al. [5]

2015

Netherlands

26,365,420

7842

1. GWAS SNP effect concordance analysis was performed between GWAS and a recent alcohol dependence GWAS using DSM-IV diagnosis. The twin-based heritability of alcohol dependence-AUDIT was estimated at 60% (55–69%).

2. GCTA showed that common SNPs jointly capture 33% of this heritability.

3. The top hits were positioned within 4 regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019.

Polimanti R et al. [11]

2017

USA

26,458,734

5546

1. In the stage 1 sample, they observed 3 GWS SNP associations, rs200889048 and rs12490016 in EAs and rs1630623 in AAs and EAs meta-analyzed.

2. In the stage 2 sample, they replicated 278, 253 and 168 of the stage 1 suggestive loci in AAs, EAs, and AAs and EAs meta-analyzed, respectively. A meta-analysis of stage 1 and stage 2 samples identified 2 additional GWS signals: rs28562191 in EAs and rs56950471 in AAs

Meyers JL et al. [9]

2017

USA

28,070,124

2382

1. Ten correlated SNPs located in an intergenic region on chromosome 3q26 were associated with fast beta (20–28 Hz) EEG power at P < 5 × 10–8. The most significantly associated SNP, rs11720469 is an expression quantitative trait locus for butyrylcholinesterase, expressed in thalamus tissue.

2. Four of the genome-wide SNPs were also associated with alcohol dependence, and two (rs13093097, rs7428372) were replicated in an independent AA sample.

3. Analyses in the AA adolescent/young adult subsample indicated association of rs11720469 with heavy episodic drinking (frequency of consuming 5+ drinks within 24 h).

Phenome-wide association studies

Polimanti R et al. [10]

2016

USA

27,187,070

26,394

1. They replicated prior associations with drinking behaviors and identified multiple novel phenome-wide significant and suggestive findings related to psychological traits, socioeconomic status, vascular/metabolic conditions, and reproductive health.

2. They applied Bayesian network learning algorithms to provide insight into the causative relationships of the novel ADH1B associations: ADH1B appears to affect phenotypic traits via both alcohol-mediated and alcohol-independent effects. They replicated the novel ADH1B associations related to socioeconomic status (household gross income and highest grade finished in school).

3. For CHRNA3-CHRNA5 risk alleles, they replicated association with smoking behaviors, lung cancer, and asthma. There were also novel suggestive CHRNA3-CHRNA5 findings with respect to high-cholesterol-medication use and distrustful attitude.