Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges

Agrawal, Arpana; Freedman, Neal D.; Cheng, Yu‐Ching; Lin, Peng; Shaffer, John R.; Sun, Qi; Taylor, Kira C.; Yaspan, Brian L.; Cole, John W.; Cornelis, Marilyn C.; DeSensi, Rebecca; Fitzpatrick, Annette L.; Heiss, Gerardo; Kang, Jae H.; O'Connell, Jeffrey; Bennett, Siiri N.; Bookman, Ebony; Bucholz, Kathleen K.; Caporaso, Neil E.; Crout, Richard J.; Dick, Danielle M.; Edenberg, Howard J.; Goate, Alison M.; Hesselbrock, Victor; Kittner, Steven J.; Kramer, John; Nürnberger, John I.; Qi, Lü; Rice, John P.; Schuckit, Marc A.; Dam, Rob M. van; Boerwinkle, Eric; Hu, Frank B.; Levy, Steven M.; Marazita, Mary L.; Mitchell, Braxton D.; Pasquale, Louis R.; Bierut, Laura J.

doi:10.3945/ajcn.111.015545

Cited by 38 publications

(28 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Further fine mapping and functional analyses are necessary to investigate the causal variant in the region of 12q24. In European populations, there were few variants associated with alcohol consumption approaching the genome-wide significance (28). A large-scale meta-analysis (of .47,000 individuals of European ancestry) identified the SNP rs6943555 in AUTS2 to be associated with alcohol consumption (daily alcohol intake; P = 4.1 3 10 29 ) (14).…”

Section: Discussionmentioning

confidence: 99%

Common variants at 12q24 are associated with drinking behavior in Han Chinese

Yang

Lu²,

Wang³

et al. 2013

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

Background: Alcohol consumption is heritable, but genetic susceptibility to drinking behavior has not been investigated widely in genome-wide association studies. Objective: We aimed to identify susceptibility loci for drinking behavior (drinkers compared with nondrinkers) in Han Chinese. Design: We performed 2 genome-wide association studies including 1420 drinkers and 3590 nondrinkers in discovery, followed by a de novo replication analysis comprising 4896 drinkers and 13,293 nondrinkers. DNA samples of the subjects were collected for genotyping. Results: The association results of drinking behavior (drinkers or nondrinkers) showed a cluster of single nucleotide polymorphisms at 12q24 in discovery (P , 5 3 10 28 ), with the strongest association for rs11066280 near C12orf51 (P-combined = 3.26 3 10 2215 ). Moreover, we observed the association with drinking behavior for a functional variant in ALDH2 at 12q24 (rs671, P-discovery = 5.17 3 10 235 ). We also identified the association between rs11066280 and daily alcohol intake among drinkers (P-combined = 4.01 3 10 221 ). Conclusion: Our data indicate that common variants at 12q24 may contribute to the susceptibility of drinking behavior in Han Chinese.Am J Clin Nutr 2013;97:545-51. Sciences and Technology,

show abstract

Section: Discussionmentioning

confidence: 99%

Common variants at 12q24 are associated with drinking behavior in Han Chinese

Yang

Lu²,

Wang³

et al. 2013

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

show abstract

“…Perhaps the accumulation of additional data will reveal conditions under which all three phenotypes share strong genetic consistency, or perhaps not. Human drinking patterns are distinctly heterogeneous, and this greatly complicates attempts at complex trait data analysis [26]. Our best hope is that progress toward elucidating genetic contributions will advance in parallel in the human genetics and genetic animal models literature and that practitioners from both camps will continue to attend to the other [27].…”

Section: Discussionmentioning

confidence: 99%

Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

et al. 2012

View full text Add to dashboard Cite

Individual mice differ in the dose of ethanol they will ingest voluntarily when it is offered during limited access periods in the circadian dark, a phenotype called drinking in the dark (DID). Substantial genetic variation in DID has been reported across a few standard inbred mouse strains, and a line of High Drinking in the Dark (HDID) mice has been established through selective breeding on the blood ethanol concentration (BEC) they attain at the end of a drinking session. Here, we report ethanol DID data for 23 inbred mouse strains, including 11 not previously reported, corroborating the genetic contributions to this trait. We also report data on a different ethanol drinking trait, the increased intake seen after multiple cycles of chronic intermittent exposure to ethanol vapor (CIE). Drinking escalated significantly during ethanol withdrawal. However, HDID mice and their HS controls showed equivalent escalation during withdrawal, demonstrating that withdrawal-associated drinking escalation is not a clear genetic correlate of selection on DID. Across inbred strains, DID is substantially genetically correlated with previously-published two-bottle ethanol preference drinking data assessed under conditions of continuous ethanol access. Although inbred strain data for withdrawal-associated drinking are not available, the current pattern of results suggests that withdrawal-associated drinking is genetically distinct from DID, while genetic contributions to DID and two-bottle preference drinking are substantially similar.

show abstract

“…In addition to genes centrally related to dopaminergic signaling that have been previously identified (e.g., ANKK1/DDRD2 , DRD1 , and DBH ) (Clarke et al, 2014; de los Cobos et al, 2007; Garrido et al, 2011; Hoenicka et al, 2010), the specific variant encoding the μ-opioid receptor ( OPRM1 , rs1799971, A118G) has frequently been associated with opioid dependence. However, a meta-analysis failed to detect a significant association between this OPRM1 marker and opioid dependence (Agrawal et al, 2012). Further, these genes have not been significantly represented in GWAS studies.…”

Section: Genetic Association Studiesmentioning

confidence: 99%

The genetic epidemiology of substance use disorder: A review

Prom‐Wormley

Ebejer

Dick

et al. 2017

Drug and Alcohol Dependence

127

View full text Add to dashboard Cite

Background Substance use disorder (SUD) remains a significant public health issue. A greater understanding of how genes and environment interact to regulate phenotypes comprising SUD will facilitate directed treatments and prevention. Methods The literature studying the neurobiological correlates of SUD with a focus on the genetic and environmental influences underlying these mechanisms was reviewed. Results from twin/family, human genetic association, gene-environment interaction, epigenetic literature, phenome-wide association studies are summarized for alcohol, nicotine, cannabinoids, cocaine, and opioids. Results There are substantial genetic influences on SUD that are expected to influence multiple neurotransmission pathways, and these influences are particularly important within the dopaminergic system. Genetic influences involved in other aspects of SUD etiology including drug processing and metabolism are also identified. Studies of gene-environment interaction emphasize the importance of environmental context in SUD. Epigenetic studies indicate drug-specific changes in gene expression as well as differences in gene expression related to the use of multiple substances. Further, gene expression is expected to differ by stage of SUD such as substance initiation versus chronic substance use. While a substantial literature has developed for alcohol and nicotine use disorders, there is comparatively less information for other commonly abused substances. Conclusions A better understanding of genetically-mediated mechanisms involved in the neurobiology of SUD provides increased opportunity to develop behavioral and biologically based treatment and prevention of SUD.

show abstract

Measuring alcohol consumption for genomic meta-analyses of alcohol intake: opportunities and challenges

Cited by 38 publications

References 68 publications

Common variants at 12q24 are associated with drinking behavior in Han Chinese

Common variants at 12q24 are associated with drinking behavior in Han Chinese

Ethanol Withdrawal-Associated Drinking and Drinking in the Dark: Common and Discrete Genetic Contributions

The genetic epidemiology of substance use disorder: A review

Contact Info

Product

Resources

About