ArticleHuman genetics2013
Association, interaction, and replication analysis of genes encoding serotonin transporter and 5-HT3 receptor subunits A and B in alcohol dependence.
Article in Human genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- A randomized, double-blind, placebo-controlled, pharmacogenetic study of ondansetron for treating alcohol use disorder.Alcoholism, clinical and experimental research · 2022Trial
- Determination of genotype combinations that can predict the outcome of the treatment of alcohol dependence using the 5-HT(3) antagonist ondansetron.The American journal of psychiatry · 2013Trial
- Multi-step gene set analysis identified HTR3 family genes involving childhood acute lymphoblastic leukemia susceptibility.Archives of toxicology · 2025Article
- The role of brain serotonin signaling in excessive alcohol consumption and withdrawal: A call for more research in females.Neurobiology of stress · 2024Article
- Sex-dependent factors of alcohol and neuroimmune mechanisms.Neurobiology of stress · 2023Article
- Alcohol Use Disorder: Neurobiology and Therapeutics.Biomedicines · 2022Review
- Serotonin ReceptorInternational journal of environmental research and public health · 2022Article
- Tapping into 5-HTInternational journal of molecular sciences · 2021Review
- Parental drinking according to parental composition and adolescent binge drinking: findings from a nationwide high school survey in Japan.BMC public health · 2020Article
- Flying Together:International journal of molecular sciences · 2020Review
- Article
- Genetic, Psychological, and Personal Network Factors Associated With Changes in Binge Drinking Over 2 Years Among Mexican Heritage Adolescents in the USA.Annals of behavioral medicine : a publication of the Society of Behavioral Medicine · 2019Article
- Association and cis-mQTL analysis of variants in serotonergic genes associated with nicotine dependence in Chinese Han smokers.Translational psychiatry · 2018Article
- Promising pharmacogenetic targets for treating alcohol use disorder: evidence from preclinical models.Pharmacogenomics · 2017Review
- Effects of Recent Stress and Variation in the Serotonin Transporter Polymorphism (5-HTTLPR) on Depressive Symptoms: A Repeated-Measures Study of Adults Age 50 and Older.Behavior genetics · 2016Article
- Association and interaction analyses of 5-HT3 receptor and serotonin transporter genes with alcohol, cocaine, and nicotine dependence using the SAGE data.Human genetics · 2014Article
- Genetics and genomics of alcohol sensitivity.Molecular genetics and genomics : MGG · 2014Review
- Genetic influences on the development of alcoholism.Current psychiatry reports · 2013Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
On the basis of the converging evidence showing regulation of drinking behavior by 5-HT3AB receptors and the serotonin transporter, we hypothesized that the interactive effects of genetic variations in the genes HTR3A, HTR3B, and SLC6A4 confer greater susceptibility to alcohol dependence (AD) than do their effects individually. We examined the associations of AD with 22 SNPs across HTR3A, HTR3B, and two functional variants in SLC6A4 in 500 AD and 280 healthy control individuals of European descent. We found that the alleles of the low-frequency SNPs rs33940208:T in HTR3A and rs2276305:A in HTR3B were inversely and nominally significantly associated with AD with odds ratio (OR) and 95 % confidence interval of 0.212 and 0.073, 0.616 (P = 0.004) and 0.261 and 0.088, 0.777 (P = 0.016), respectively. Further, our gene-by-gene interaction analysis revealed that two four-variant models that differed by only one SNP carried a risk for AD (empirical P < 1 × 10(-6) for prediction accuracy of the two models based on 10(6) permutations). Subsequent analysis of these two interaction models revealed an OR of 2.71 and 2.80, respectively, for AD (P < 0.001) in carriers of genotype combinations 5'-HTTLPR:LL/LS(SLC6A4)-rs1042173:TT/TG(SLC6A4)-rs1176744:AC(HTR3B)-rs3782025:AG(HTR3B) and 5'-HTTLPR:LL/LS(SLC6A4)-rs10160548:GT/TT(HTR3A)-rs1176744:AC(HTR3B)-rs3782025:AG(HTR3B). Combining all five genotypes resulted in an OR of 3.095 (P = 2.0 × 10(-4)) for AD. Inspired by these findings, we conducted the analysis in an independent sample, OZ-ALC-GWAS (N = 6699), obtained from the NIH dbGAP database, which confirmed the findings, not only for all three risk genotype combinations (Z = 4.384, P = 1.0 × 10(-5); Z = 3.155, P = 1.6 × 10(-3); and Z = 3.389, P = 7.0 × 10(-4), respectively), but also protective effects for rs33940208:T (χ (2) = 3.316, P = 0.0686) and rs2276305:A (χ (2) = 7.224, P = 0.007). These findings reveal significant interactive effects among variants in SLC6A4-HTR3A-HTR3B affecting AD. Further studies are needed to confirm these findings and characterize the molecular mechanisms underlying these effects.
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