Genome‐Wide Association Study of Alcohol Dependence Implicates a Region on Chromosome 11

Edenberg, Howard J.; Koller, Daniel L.; Xuei, Xiaoling; Wetherill, Leah; McClintick, Jeanette N.; Almasy, Laura; Bierut, Laura J.; Bucholz, Kathleen K.; Goate, Alison M.; Alıev, Fazil; Dick, Danielle M.; Hesselbrock, Victor; Hinrichs, Anthony L.; Kramer, John; Kuperman, Samuel; Nürnberger, John I.; Rice, John P.; Schuckit, Marc A.; Taylor, Robert E.; Webb, Bradley T.; Tischfield, Jay A.; Porjesz, Bernice; Foroud, Tatiana

doi:10.1111/j.1530-0277.2010.01156.x

Cited by 279 publications

(304 citation statements)

References 70 publications

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“…Accordingly, any single gene contributes only to a limited extent to the phenotypes observed in alcohol consumption (6). In contrast to alcohol addiction, which has been investigated in numerous genetic studies (5), including recent genome-wide association studies (GWAS) analyses (7)(8)(9), few genes regulating alcohol consumption in humans have been described-with the notable exception of alcohol dehydrogenase (3,5,10). This may, to some extent, reflect the complexity of the phenotype, because the genetic and environmental determinants of alcohol drinking behavior may vary over the lifespan, and there may be substantial heterogeneity of intake and measurement across different populations and studies.…”

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confidence: 99%

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene ( AUTS2 ) in the regulation of alcohol consumption

Schumann

Coin

Lourdusamy

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Alcohol consumption is a moderately heritable trait, but the genetic basis in humans is largely unknown, despite its clinical and societal importance. We report a genome-wide association study meta-analysis of ∼2.5 million directly genotyped or imputed SNPs with alcohol consumption (gram per day per kilogram body weight) among 12 population-based samples of European ancestry, comprising 26,316 individuals, with replication genotyping in an additional 21,185 individuals. SNP rs6943555 in autism susceptibility candidate 2 gene ( AUTS2 ) was associated with alcohol consumption at genome-wide significance ( P = 4 × 10 −8 to P = 4 × 10 −9 ). We found a genotype-specific expression of AUTS2 in 96 human prefrontal cortex samples ( P = 0.026) and significant ( P < 0.017) differences in expression of AUTS2 in whole-brain extracts of mice selected for differences in voluntary alcohol consumption. Down-regulation of an AUTS2 homolog caused reduced alcohol sensitivity in Drosophila ( P < 0.001). Our finding of a regulator of alcohol consumption adds knowledge to our understanding of genetic mechanisms influencing alcohol drinking behavior.

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confidence: 99%

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene ( AUTS2 ) in the regulation of alcohol consumption

Schumann

Coin

Lourdusamy

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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259

258

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“…A second strategy is to narrow the phenotype and to analyze a more homogeneous sample. A GWAS analysis was performed on the COGA subset of European-American subjects (996 subjects overlap with this report) (32). This approach focuses the analysis on subjects recruited under a single ascertainment protocol for alcohol dependence, and the severity of illness in these subjects is high.…”

Section: Discussionmentioning

confidence: 99%

A genome-wide association study of alcohol dependence

Bierut

Agrawal

Bucholz

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10 −5 , but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2 , which encodes the GABA receptor α2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

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“…7,10,11 The relevant role of genetic factors both on alcohol consumption and dependence has been clearly demonstrated by genome-wide association study (GWAS) studies. [12][13][14][15][16] Moreover, studies on the genetic variations in bitter taste receptors have also shown that variations in TAS2R16 and TAS2R38 genes can influence alcohol intake [17][18][19] but not dependence. 19 On the contrary, very little is known about the possible contribution of genetic factors to alcohol preferences in humans.…”

Section: Introductionmentioning

confidence: 99%

Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

Pirastu

Kooyman

Traglia³

et al. 2015

Eur J Hum Genet

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Wine is the most popular alcoholic beverage around the world and because of its importance in society has been widely studied. Understanding what drives its flavor has been a quest for decades but much is still unknown and will be determined at least in part by individual taste preferences. Recently studies in the genetics of taste have uncovered the role of different genes in the determination of food preferences giving new insight on its physiology. In this context we have performed a genome-wide association study on red and white wine liking using three isolated populations collected in Italy, and replicated our results on two additional populations coming from the Netherland and Central Asia for a total of 3885 samples. We have found a significant association (P = 2.1 × 10 − 8 ) between white wine liking and rs9276975:C4T a polymorphism in the HLA-DOA gene encoding a non-canonical MHC II molecule, which regulates other MHC II molecules. The same association was also found with red wine liking (P = 8.3 × 10 − 6 ). Sex-separated analysis have also revealed that the effect of HLA-DOA is twice as large in women as compared to men suggesting an interaction between this polymorphism and gender. Our results are one of the first examples of genome-wide association between liking of a commonly consumed food and gene variants. Moreover, our results suggest a role of the MHC system in the determination of food preferences opening new insight in this field in general. INTRODUCTIONWine is probably the oldest produced beverage in human history dating its first apparition in Georgia 7000 BC. It is extremely important for many cultures not only for its economy but also from the social and religious point of view. For these reasons it is also the most common and consumed type of alcoholic beverage throughout the world. 1,2 In addition, several studies indicate that modest wine consumption can have some beneficial health effects, including protection against cardiovascular and Alzheimer's disease. [3][4][5][6] There has been extensive research aiming to improve both its production and its flavor. The taste of wine depends on many different sensory perceptions ranging from taste and olfaction to texture. 7 Wine is a mixture of thousands of molecules that can contribute to its final taste, 8 and its composition varies greatly depending on the grapes used, climate and production method. 9 Although the flavor of some of these compounds is very well known, it is really difficult to understand what their role in final taste is. 7,10,11 The relevant role of genetic factors both on alcohol consumption and dependence has been clearly demonstrated by genome-wide association study (GWAS) studies. [12][13][14][15][16] Moreover, studies on the genetic variations in bitter taste receptors have also shown that variations in TAS2R16 and TAS2R38 genes can influence alcohol intake [17][18][19] but not dependence. 19 On the contrary, very little is known about the possible contribution of genetic factors to alcohol preferences in humans. Recen...

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Genome‐Wide Association Study of Alcohol Dependence Implicates a Region on Chromosome 11

Abstract: Background: Alcohol dependence is a complex disease, and although linkage and candidate gene studies have identified several genes associated with the risk for alcoholism, these explain only a portion of the risk.

Cited by 279 publications

References 70 publications

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene ( AUTS2 ) in the regulation of alcohol consumption

Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene ( AUTS2 ) in the regulation of alcohol consumption

A genome-wide association study of alcohol dependence

Genome-wide association analysis on five isolated populations identifies variants of the HLA-DOA gene associated with white wine liking

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