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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.