Human Genetics of Addiction: New Insights and Future Directions

Hancock, Dana B.; Markunas, Christina A.; Bierut, Laura J.; Johnson, Eric O.

doi:10.1007/s11920-018-0873-3

Cited by 100 publications

(84 citation statements)

References 154 publications

(186 reference statements)

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“…For highly complex diseases like addiction that are influenced by vast numbers of genetic variants, population‐based genome‐wide association approaches are better suited to identify risk loci with relatively small effects compared with family‐based genetic studies, but the sample size requirements are substantial. Early studies suffered from low genetic marker density, but increased power and precision in subsequent studies has allowed identification of some causal genes .…”

Section: Human Genetic Studies Of Sex Differences In Addictionmentioning

confidence: 99%

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Datta

Schoenrock

Bubier

et al. 2020

Genes Brain and Behavior

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Despite substantial evidence for sex differences in addiction epidemiology, addiction‐relevant behaviors and associated neurobiological phenomena, the mechanisms and implications of these differences remain unknown. Genetic analysis in model organism is a potentially powerful and effective means of discovering the mechanisms that underlie sex differences in addiction. Human genetic studies are beginning to show precise risk variants that influence the mechanisms of addiction but typically lack sufficient power or neurobiological mechanistic access, particularly for the discovery of the mechanisms that underlie sex differences. Our thesis in this review is that genetic variation in model organisms are a promising approach that can complement these investigations to show the biological mechanisms that underlie sex differences in addiction.

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Section: Human Genetic Studies Of Sex Differences In Addictionmentioning

confidence: 99%

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Datta

Schoenrock

Bubier

et al. 2020

Genes Brain and Behavior

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“…Other reviews have elegantly summarized findings from twin and family studies of heritability, linkage, candidate gene and GWAS [e.g. (3)(4)(5)(6)], and we extend on recent reviews of the molecular genetics of AUD (7-9) by 4 including additional GWAS of alcohol use behaviors that identify genome-wide significant hits (P-value < 5 x 10 -8 ). In addition, we discuss the application of polygenic methods, which provide mounting evidence that alcohol use and misuse are partially distinct.…”

Section: Introductionmentioning

confidence: 99%

Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse

Sanchez‐Roige

Palmer

Clarke

2020

Biological Psychiatry

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Alcohol use disorders (AUD) are defined by several symptom criteria, which can be further dissected at the genetic level. Over the past several years, our understanding of the genetic factors influencing alcohol use and abuse has progressed tremendously; hundreds of loci have now been implicated in different aspects of alcohol use. Previously known associations with alcohol metabolizing enzymes (ADH1B, ALDH2) have been definitively replicated. Additionally, novel associations with loci containing the genes KLB, GCKR, CRHR1 and CADM2 have been reported. Downstream analyses have leveraged these genetic findings to reveal important relationships between alcohol use behaviors and both physical and mental health. AUD and aspects of alcohol misuse have been shown to overlap strongly with psychiatric disorders, whereas aspects of alcohol consumption have shown stronger links to metabolism. These results demonstrate that the genetic architecture of alcohol consumption only partially overlaps with the genetics of clinically defined AUD. We discuss the limitations of using quantitative measures of alcohol use as proxy measures for AUD, and outline how future studies will require careful phenotype harmonization to properly capture the genetic liability to AUD.

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“…Only six reproducible, genome-wide significant loci have been identified: CHRNB3-CHRNA6 (chr8p11), DBH (chr9q34), CHRNA5-CHRNA3-CHRNB4 (chr15q25), DNMT3B and NOL4L (chr20q11), and CHRNA4 (chr20q13). 6 A more complete understanding of the genetics underlying ND is needed, as it could help to predict the likelihood of quitting smoking, withdrawal severity, response to treatment, and health-related consequences. [7][8][9][10] The Fagerström Test for ND (FTND), also called the Fagerström Test for Cigarette Dependence, 11 provides a composite phenotype that captures multiple behavioral and psychological features of ND among smokers.…”

Section: Introductionmentioning

confidence: 99%

Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium

Quach

Bray

Gaddis

et al. 2020

Preprint

Self Cite

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AbstractCigarette smoking is the leading cause of preventable morbidity and mortality. Knowledge is evolving on genetics underlying initiation, regular smoking, nicotine dependence (ND), and cessation. We performed a genome-wide association study using the Fagerström Test for ND (FTND) in 58,000 smokers of European or African ancestry. Five genome-wide significant loci, including two novel loci MAGI2/GNAI1 (rs2714700) and TENM2 (rs1862416) were identified, and loci reported for other smoking traits were extended to ND. Using the heaviness of smoking index (HSI) in the UK Biobank (N=33,791), rs2714700 was consistently associated, but rs1862416 was not associated, likely reflecting ND features not captured by the HSI. Both variants were cis-eQTLs (rs2714700 for MAGI2-AS3 in hippocampus, rs1862416 for TENM2 in lung), and expression of genes spanning ND-associated variants was enriched in cerebellum. SNP-based heritability of ND was 8.6%, and ND was genetically correlated with 17 other smoking traits (rg=0.40–0.95) and co-morbidities. Our results emphasize the FTND as a composite phenotype that expands genetic knowledge of smoking, including loci specific to ND.

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Human Genetics of Addiction: New Insights and Future Directions

Cited by 100 publications

References 154 publications

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis

Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse

Expanding the Genetic Architecture of Nicotine Dependence and its Shared Genetics with Multiple Traits: Findings from the Nicotine Dependence GenOmics (iNDiGO) Consortium

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