Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures

M. Kapoor, Y. L. Chou, Howard Edenberg, Tatiana Foroud, N. G. Martin, P. A F Madden, J. C. Wang, S. Bertelsen, L. Wetherill, A. Brooks, G. Chan, V. Hesselbrock, S. Kuperman, S. E. Medland, G. Montgomery, J. Tischfield, J. B. Whitfield, L. J. Bierut, A. C. Heath, K. K. BucholzA. M. Goate, A. Agrawal

Research output: Contribution to journalArticle

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Abstract

Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.

Original languageEnglish (US)
Pages (from-to)e761
JournalTranslational Psychiatry
Volume6
DOIs
StatePublished - Mar 22 2016

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Age of Onset
Alcoholism
Alcohols
Genome
Genome-Wide Association Study
Alcohol Drinking
Drinking
Single Nucleotide Polymorphism
Pedigree
Phenotype

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures. / Kapoor, M.; Chou, Y. L.; Edenberg, Howard; Foroud, Tatiana; Martin, N. G.; Madden, P. A F; Wang, J. C.; Bertelsen, S.; Wetherill, L.; Brooks, A.; Chan, G.; Hesselbrock, V.; Kuperman, S.; Medland, S. E.; Montgomery, G.; Tischfield, J.; Whitfield, J. B.; Bierut, L. J.; Heath, A. C.; Bucholz, K. K.; Goate, A. M.; Agrawal, A.

In: Translational Psychiatry, Vol. 6, 22.03.2016, p. e761.

Research output: Contribution to journalArticle

Kapoor, M, Chou, YL, Edenberg, H, Foroud, T, Martin, NG, Madden, PAF, Wang, JC, Bertelsen, S, Wetherill, L, Brooks, A, Chan, G, Hesselbrock, V, Kuperman, S, Medland, SE, Montgomery, G, Tischfield, J, Whitfield, JB, Bierut, LJ, Heath, AC, Bucholz, KK, Goate, AM & Agrawal, A 2016, 'Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures', Translational Psychiatry, vol. 6, pp. e761. https://doi.org/10.1038/tp.2016.27
Kapoor, M. ; Chou, Y. L. ; Edenberg, Howard ; Foroud, Tatiana ; Martin, N. G. ; Madden, P. A F ; Wang, J. C. ; Bertelsen, S. ; Wetherill, L. ; Brooks, A. ; Chan, G. ; Hesselbrock, V. ; Kuperman, S. ; Medland, S. E. ; Montgomery, G. ; Tischfield, J. ; Whitfield, J. B. ; Bierut, L. J. ; Heath, A. C. ; Bucholz, K. K. ; Goate, A. M. ; Agrawal, A. / Genome-wide polygenic scores for age at onset of alcohol dependence and association with alcohol-related measures. In: Translational Psychiatry. 2016 ; Vol. 6. pp. e761.
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abstract = "Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7{\%} of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16{\%}. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.",
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AU - Kapoor, M.

AU - Chou, Y. L.

AU - Edenberg, Howard

AU - Foroud, Tatiana

AU - Martin, N. G.

AU - Madden, P. A F

AU - Wang, J. C.

AU - Bertelsen, S.

AU - Wetherill, L.

AU - Brooks, A.

AU - Chan, G.

AU - Hesselbrock, V.

AU - Kuperman, S.

AU - Medland, S. E.

AU - Montgomery, G.

AU - Tischfield, J.

AU - Whitfield, J. B.

AU - Bierut, L. J.

AU - Heath, A. C.

AU - Bucholz, K. K.

AU - Goate, A. M.

AU - Agrawal, A.

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N2 - Age at onset of alcohol dependence (AO-AD) is a defining feature of multiple drinking typologies. AO-AD is heritable and likely shares genetic liability with other aspects of alcohol consumption. We examine whether polygenic variation in AO-AD, based on a genome-wide association study (GWAS), was associated with AO-AD and other aspects of alcohol consumption in two independent samples. Genetic risk scores (GRS) were created based on AO-AD GWAS results from a discovery sample of 1788 regular drinkers from extended pedigrees from the Collaborative Study of the Genetics of Alcoholism (COGA). GRS were used to predict AO-AD, AD and Alcohol dependence symptom count (AD-SX), age at onset of intoxication (AO-I), as well as maxdrinks in regular drinking participants from two independent samples-the Study of Addictions: Genes and Environment (SAGE; n=2336) and an Australian sample (OZ-ALC; n=5816). GRS for AO-AD from COGA explained a modest but significant proportion of the variance in all alcohol-related phenotypes in SAGE. Despite including effect sizes associated with large numbers of single nucleotide polymorphisms (SNPs; >110 000), GRS explained, at most, 0.7% of the variance in these alcohol measures in this independent sample. In OZ-ALC, significant but even more modest associations were noted with variance estimates ranging from 0.03 to 0.16%. In conclusion, there is modest evidence that genetic variation in AO-AD is associated with liability to other aspects of alcohol involvement.

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