Manuel Mattheisen

Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. / Zhou, Hang; Sealock, Julia M; Sanchez-Roige, Sandra; Clarke, Toni-Kim; Levey, Daniel F; Cheng, Zhongshan; Li, Boyang; Polimanti, Renato; Kember, Rachel L; Smith, Rachel Vickers; Thygesen, Johan H; Morgan, Marsha Y; Atkinson, Stephen R; Thursz, Mark R; Nyegaard, Mette; Mattheisen, Manuel; Børglum, Anders D; Johnson, Emma C; Justice, Amy C; Palmer, Abraham A; McQuillin, Andrew; Davis, Lea K; Edenberg, Howard J; Agrawal, Arpana; Kranzler, Henry R; Gelernter, Joel.

In: Nature Neuroscience, Vol. 23, No. 7, 07.2020, p. 809-818.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Zhou, H, Sealock, JM, Sanchez-Roige, S, Clarke, T-K, Levey, DF, Cheng, Z, Li, B, Polimanti, R, Kember, RL, Smith, RV, Thygesen, JH, Morgan, MY, Atkinson, SR, Thursz, MR, Nyegaard, M, Mattheisen, M, Børglum, AD, Johnson, EC, Justice, AC, Palmer, AA, McQuillin, A, Davis, LK, Edenberg, HJ, Agrawal, A, Kranzler, HR & Gelernter, J 2020, 'Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits', Nature Neuroscience, vol. 23, no. 7, pp. 809-818. https://doi.org/10.1038/s41593-020-0643-5

APA

Zhou, H., Sealock, J. M., Sanchez-Roige, S., Clarke, T-K., Levey, D. F., Cheng, Z., Li, B., Polimanti, R., Kember, R. L., Smith, R. V., Thygesen, J. H., Morgan, M. Y., Atkinson, S. R., Thursz, M. R., Nyegaard, M., Mattheisen, M., Børglum, A. D., Johnson, E. C., Justice, A. C., ... Gelernter, J. (2020). Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience, 23(7), 809-818. https://doi.org/10.1038/s41593-020-0643-5

CBE

Zhou H, Sealock JM, Sanchez-Roige S, Clarke T-K, Levey DF, Cheng Z, Li B, Polimanti R, Kember RL, Smith RV, Thygesen JH, Morgan MY, Atkinson SR, Thursz MR, Nyegaard M, Mattheisen M, Børglum AD, Johnson EC, Justice AC, Palmer AA, McQuillin A, Davis LK, Edenberg HJ, Agrawal A, Kranzler HR, Gelernter J. 2020. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience. 23(7):809-818. https://doi.org/10.1038/s41593-020-0643-5

MLA

Vancouver

Zhou H, Sealock JM, Sanchez-Roige S, Clarke T-K, Levey DF, Cheng Z et al. Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. Nature Neuroscience. 2020 Jul;23(7):809-818. https://doi.org/10.1038/s41593-020-0643-5

Author

Zhou, Hang ; Sealock, Julia M ; Sanchez-Roige, Sandra ; Clarke, Toni-Kim ; Levey, Daniel F ; Cheng, Zhongshan ; Li, Boyang ; Polimanti, Renato ; Kember, Rachel L ; Smith, Rachel Vickers ; Thygesen, Johan H ; Morgan, Marsha Y ; Atkinson, Stephen R ; Thursz, Mark R ; Nyegaard, Mette ; Mattheisen, Manuel ; Børglum, Anders D ; Johnson, Emma C ; Justice, Amy C ; Palmer, Abraham A ; McQuillin, Andrew ; Davis, Lea K ; Edenberg, Howard J ; Agrawal, Arpana ; Kranzler, Henry R ; Gelernter, Joel. / Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits. In: Nature Neuroscience. 2020 ; Vol. 23, No. 7. pp. 809-818.

Bibtex

@article{dcd9042609de4906b010d7e13038f4c5,
title = "Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits",
abstract = "Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.",
keywords = "ASSOCIATION, BIOBANK, DEPENDENCE, DISORDER, GWAS, HERITABILITY, LD SCORE REGRESSION, LOCI, MENDELIAN RANDOMIZATION, RISK",
author = "Hang Zhou and Sealock, {Julia M} and Sandra Sanchez-Roige and Toni-Kim Clarke and Levey, {Daniel F} and Zhongshan Cheng and Boyang Li and Renato Polimanti and Kember, {Rachel L} and Smith, {Rachel Vickers} and Thygesen, {Johan H} and Morgan, {Marsha Y} and Atkinson, {Stephen R} and Thursz, {Mark R} and Mette Nyegaard and Manuel Mattheisen and B{\o}rglum, {Anders D} and Johnson, {Emma C} and Justice, {Amy C} and Palmer, {Abraham A} and Andrew McQuillin and Davis, {Lea K} and Edenberg, {Howard J} and Arpana Agrawal and Kranzler, {Henry R} and Joel Gelernter",
year = "2020",
month = jul,
doi = "10.1038/s41593-020-0643-5",
language = "English",
volume = "23",
pages = "809--818",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "7",

}

RIS

TY - JOUR

T1 - Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits

AU - Zhou, Hang

AU - Sealock, Julia M

AU - Sanchez-Roige, Sandra

AU - Clarke, Toni-Kim

AU - Levey, Daniel F

AU - Cheng, Zhongshan

AU - Li, Boyang

AU - Polimanti, Renato

AU - Kember, Rachel L

AU - Smith, Rachel Vickers

AU - Thygesen, Johan H

AU - Morgan, Marsha Y

AU - Atkinson, Stephen R

AU - Thursz, Mark R

AU - Nyegaard, Mette

AU - Mattheisen, Manuel

AU - Børglum, Anders D

AU - Johnson, Emma C

AU - Justice, Amy C

AU - Palmer, Abraham A

AU - McQuillin, Andrew

AU - Davis, Lea K

AU - Edenberg, Howard J

AU - Agrawal, Arpana

AU - Kranzler, Henry R

AU - Gelernter, Joel

PY - 2020/7

Y1 - 2020/7

N2 - Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.

AB - Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. Although genome-wide association studies have identified PAU risk genes, the genetic architecture of this trait is not fully understood. We conducted a proxy-phenotype meta-analysis of PAU, combining alcohol use disorder and problematic drinking, in 435,563 European-ancestry individuals. We identified 29 independent risk variants, 19 of them novel. PAU was genetically correlated with 138 phenotypes, including substance use and psychiatric traits. Phenome-wide polygenic risk score analysis in an independent biobank sample (BioVU, n = 67,589) confirmed the genetic correlations between PAU and substance use and psychiatric disorders. Genetic heritability of PAU was enriched in brain and in conserved and regulatory genomic regions. Mendelian randomization suggested causal effects on liability to PAU of substance use, psychiatric status, risk-taking behavior and cognitive performance. In summary, this large PAU meta-analysis identified novel risk loci and revealed genetic relationships with numerous other traits.

KW - ASSOCIATION

KW - BIOBANK

KW - DEPENDENCE

KW - DISORDER

KW - GWAS

KW - HERITABILITY

KW - LD SCORE REGRESSION

KW - LOCI

KW - MENDELIAN RANDOMIZATION

KW - RISK

U2 - 10.1038/s41593-020-0643-5

DO - 10.1038/s41593-020-0643-5

M3 - Journal article

C2 - 32451486

VL - 23

SP - 809

EP - 818

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 7

ER -