Multivariate analysis of 1.5 million people identifies genetic associations with traits related to self-regulation and addiction

被引：182

作者：

Linner, Richard Karlsson ^{[1
]}

Mallard, Travis T. ^{[2
]}

Barr, Peter B. ^{[3
]}

Sanchez-Roige, Sandra ^{[4
,5
]}

Madole, James W. ^{[2
]}

Driver, Morgan N. ^{[6
]}

Poore, Holly E. ^{[7
]}

de Vlaming, Ronald ^{[1
]}

Grotzinger, Andrew D. ^{[2
]}

Tielbeek, Jorim J. ^{[8
]}

Johnson, Emma C. ^{[9
]}

Liu, Mengzhen ^{[10
]}

Rosenthal, Sara Brin ^{[11
]}

Ideker, Trey ^{[12
]}

Zhou, Hang ^{[13
,14
]}

Kember, Rachel L. ^{[15
,16
]}

Pasman, Joelle A. ^{[17
]}

Verweij, Karin J. H. ^{[18
]}

Liu, Dajiang J. ^{[19
,20
]}

Vrieze, Scott ^{[10
]}

Kranzler, Henry R. ^{[15
,16
]}

Gelernter, Joel ^{[13
,14
,21
,22
]}

Harris, Kathleen Mullan ^{[23
,24
]}

Tucker-Drob, Elliot M. ^{[2
,25
]}

Waldman, Irwin D. ^{[7
,26
]}

Palmer, Abraham A. ^{[4
,27
]}

Harden, K. Paige ^{[2
,25
]}

Koellinger, Philipp D. ^{[1
,28
]}

Dick, Danielle M. ^{[3
,6
]}

机构：

[1] Vrije Univ Amsterdam, Dept Econ, Amsterdam, Netherlands

[2] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA

[3] Virginia Commonwealth Univ, Dept Psychol, Box 2018, Richmond, VA 23284 USA

[4] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

[5] Vanderbilt Univ, Div Genet Med, Med Ctr, Nashville, TN USA

[6] Virginia Commonwealth Univ, Dept Human & Mol Genet, Richmond, VA 23284 USA

[7] Emory Univ, Dept Psychol, Atlanta, GA 30322 USA

[8] Vrije Univ Amsterdam, Dept Complex Trait Genet, Amsterdam, Netherlands

[9] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA

[10] Univ Minnesota, Dept Psychol, Minneapolis, MN USA

[11] Univ Calif San Diego, Dept Med, Ctr Computat Biol & Bioinformat, La Jolla, CA 92093 USA

[12] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[13] Yale Univ, Dept Psychiat, Sch Med, West Haven, CT 06516 USA

[14] VA CT Healthcare Syst, Dept Psychiat, West Haven, CT USA

[15] Univ Penn, Sch Med, Ctr Studies Addict, Philadelphia, PA 19104 USA

[16] Crescenz VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA

[17] Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands

[18] Univ Amsterdam, Dept Psychiat, Amsterdam UMC, Amsterdam, Netherlands

[19] Penn State Univ, Dept Publ Hlth Sci, Hershey, PA USA

[20] Penn State Univ, Inst Personalized Med, Hershey, PA USA

[21] Yale Univ, Dept Genet, Sch Med, West Haven, CT 06516 USA

[22] Yale Univ, Sch Med, Dept Neurosci, West Haven, CT 06516 USA

[23] Univ N Carolina, Dept Sociol, Chapel Hill, NC USA

[24] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA

[25] Univ Texas Austin, Populat Res Ctr, Austin, TX 78712 USA

[26] Emory Univ, Ctr Computat & Quantitat Genet, Atlanta, GA 30322 USA

[27] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA

[28] Univ Wisconsin, La Follette Sch Publ Affairs, Madison, WI 53706 USA

来源：

NATURE NEUROSCIENCE | 2021年 / 24卷 / 10期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; PHILADELPHIA NEURODEVELOPMENTAL COHORT; ALCOHOL DEPENDENCE; VARIANTS; GWAS; HEALTH; COMMON; RISK; METAANALYSIS; ADOLESCENT;

D O I：

10.1038/s41593-021-00908-3

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Behaviors and disorders related to self-regulation, such as substance use, antisocial behavior and attention-deficit/hyperactivity disorder, are collectively referred to as externalizing and have shared genetic liability. We applied a multivariate approach that leverages genetic correlations among externalizing traits for genome-wide association analyses. By pooling data from similar to 1.5 million people, our approach is statistically more powerful than single-trait analyses and identifies more than 500 genetic loci. The loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results predicts a range of behavioral and medical outcomes that were not part of genome-wide analyses, including traits that until now lacked well-performing polygenic scores, such as opioid use disorder, suicide, HIV infections, criminal convictions and unemployment. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental trait with complex and far-reaching social and health correlates.

引用

页码：1367 / 1376

页数：10

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