TITLE Kind of study Main result REFERENCE
1 The genetics of alcohol dependence. Review Genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission are selected as best candidates for AD related genes [35]
2 Genome-wide association study of alcohol dependence:significant findings in African- and European-Americans including novel risk loci. GWAS 16,087 AD  subjects; ADH1B, ADH1C, ADH gene cluster, PDLIM5, METAP, rs1437396, between MTIF2 and CCDC88A may be associated with AD [36]
3 Family-Based Association Analysis of Alcohol Dependence Criteria and Severity. GWAS 118 extended European American families (n = 2,322 individuals); NALCN, OR51L1 may be associated with AD [37]
4 Introduction to Deep Sequencing and Its Application to Drug Addiction Research with a Focus on Rare Variants. Review ALDH2 may be associated with AD [38]
5 A genome-wide association study of behavioral disinhibition. GWAS 7,188 Caucasian individuals clustered in 2,300 nuclear families; rs1868152 (intronic) associated with the use of illicit drugs [39]
6 Association, interaction, and replication analysis of genes encoding serotonin transporter and 5-HT3 receptor subunits A and B in alcohol dependence. Candidate gene 500 AD and 280 healthy control individuals of European descent; SLC6A4-HTR3A-HTR3B interact in affecting AD [40]
7 Dosage transmission disequilibrium test (dTDT) for linkage and association detection. TDT Rs4903712 may affect AD behavior [41]
8 A meta-analysis of two genome-wide association studies to identify novel loci for maximum number of alcoholic drinks. Meta-analysis of GWAS two GWAS using maxdrinks as an excessive alcohol consumption phenotype: one in 118 extended families (N = 2,322) selected from COGA,, and the other in a case-control sample (N = 2,593) derived from SAGE.  Rs9523562 and  rs67666182 were associated with AD. LMO1, AUTS2, INADL, HIP1 and PLCL1 were associated with alcohol related phenotypes. [42]
9 Common biological networks underlie genetic risk for alcoholism in African- and European-American populations. GWAS re-analysis Chloride transporters and glycine metabolism genes are associated with AD [43]
10 Replication of genome wide association studies of alcohol dependence: support for association with variation in ADH1C. GWAS 808 alcohol-dependent cases and 1,248 controls; ADH1C may be associated with AD [44]
11 Extended genetic effects of ADH cluster genes on the risk of alcohol dependence: from GWAS to replication. GWAS ADH1B may be associated with AD [45]
12 Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-wide association study. Mixed animal and GWAS in humans approach COGA and SAGE samples; brain responses to ethanol and neural adaptations genes are involved in AD [46]
13 Using genetic information from candidate gene and genome-wide association studies in risk prediction for alcohol dependence. GWAS COGA and SAGE samples [47]
14 Genome-wide association study identifies a potent locus associated with human opioid sensitivity. GWAS Family history was a better predictor of AD than genes [48]
15 A genome-wide association study of alcohol-dependence symptom counts in extended pedigrees identifies C15orf53. GWAS Collaborative Study on the Genetics of Alcoholism  sample; C15orf53 may be associated with AD [49]
16 TACR1 genotypes predict fMRI response to alcohol cues and level of alcohol dependence. Imaging study 326 individuals with alcohol use disorders; rs3771863, rs3755459, and rs1106855 (TACR1) predicted BOLD activation in response to alcohol cues [50]
17 ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior. GWAS 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans; ANKRD7, CYTL1 may be associated with AD [51]
18 Genetic influences on craving for alcohol. Candidate gene analysis and GWAS a sample of unrelated adults ascertained for alcohol dependence (N=3976); DRD3, ITGADmay be associated with AD (craving) [52]
19 A novel, functional and replicable risk gene region for alcohol dependence identified by genome-wide association study. GWAS a discovery sample of 681 African-American (AA) cases with alcohol dependence and 508 AA controls were retested in a primary replication sample of 1,409 European-American (EA) cases and 1,518 EA controls; PHF3-PTP4A1 locus may be associated with AD [53]
20 A haplotype analysis is consistent with the role of functional HTR1B variants in alcohol dependence. Candidate study 136 Brazilian alcoholics of European descendent and 237 controls; rs11568817 (HTR1B) may be associated with AD [54]
21 Genome-wide significant association between alcohol dependence and a variant in the ADH gene cluster. GWAS 1333 male in-patients with severe AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and 2168 controls; ADH1B, ADH1C may be associated with AD [55]
22 Genome-wide association study of alcohol dependence implicates KIAA0040 on chromosome 1q. GWAS 4116 subjects (1409 European-American (EA) cases with AD, 1518 EA controls, 681 African-American (AA) cases, and 508 AA controls); TNN-KIAA0040 may be associated with AD [56]
23 A quantitative-trait genome-wide association study of alcoholism risk in the community: findings and implications. GWAS 3393 Australians with genome-wide SNP data; ANKS1A and TMEM108 may be associated with AD [57]
24 Genome-wide association study of theta band event-related oscillations identifies serotonin receptor gene HTR7 influencing risk of alcohol dependence. GWAS 1,064 unrelated individuals, ARID5A, HTR7 may be associated with event-related brain oscillations [59]
25 Genome-wide association study of alcohol dependence implicates a region on chromosome 11. GWAS Collaborative Study on the Genetics of Alcoholismsample; SLC22A18, PHLDA2, NAP1L4, SNORA54, CARS, and OSBPL5 may be associated with AD [60]
26 A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations. GWAS 1224 cases and 1162 controls plus comorbid AD and ND, 599 cases and 488 controls; ARHGAP10, MARK1, DDX6, KIAA1409 may be associated with AD or ND [61]
27 Genome-wide association study of alcohol dependence GWAS 487 male inpatients with alcohol dependence, 1358 population-based control individuals; follow-up study included 1024 male inpatients and 996 age-matched male controls. CDH13 and  ADH1C may be involved in AD [62]
The table is a resumen of the studies analyzed to extract the initial subset of genes that showed a possible association with alcohol dependence phenotypes in last 10 years. AD: Alcohol-dependence; ND: Nicotine-dependence COGA: Collaborative Study on the Genetics of Alcoholism (http://www.niaaa.nih.gov/research/major-initiatives/collaborative-studies-genetics-alcoholism-coga-study) SAGE: Study of Addiction: Genes and Environment (http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000092.v1.p1)
Table 4: Studies analyzed. The GWAS studies were used to obtain the list of genes for prioritizing the molecular cascades to be analyzed. The other articles provided material for the background and discussion.
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