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Multivariate Analysis of 1.5 Million People Identifies Genetic Associations with Traits Related to Self-Regulation and Addiction

Citation

Karlsson Linnér, Richard; Mallard, Travis T.; Barr, Peter B.; Sanchez-Roige, Sandra; Madole, James W.; Driver, Morgan N.; Poore, Holly E.; de Vlaming, Ronald; Grotzinger, Andrew D.; & Tielbeek, Jorim J., et al. (2021). Multivariate Analysis of 1.5 Million People Identifies Genetic Associations with Traits Related to Self-Regulation and Addiction. Nature Neuroscience, 24(10), 1367-1376. PMCID: PMC8484054

Abstract

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 ~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.

URL

http://dx.doi.org/10.1038/s41593-021-00908-3

Reference Type

Journal Article

Year Published

2021

Journal Title

Nature Neuroscience

Author(s)

Karlsson Linnér, Richard
Mallard, Travis T.
Barr, Peter B.
Sanchez-Roige, Sandra
Madole, James W.
Driver, Morgan N.
Poore, Holly E.
de Vlaming, Ronald
Grotzinger, Andrew D.
Tielbeek, Jorim J.
Johnson, Emma C.
Liu, Mengzhen
Rosenthal, Sara Brin
Ideker, Trey
Zhou, Hang
Kember, Rachel L.
Pasman, Joëlle A.
Verweij, Karin J. H.
Liu, Dajiang J.
Vrieze, Scott
COGA Collaborators,
Kranzler, Henry R.
Gelernter, Joel E.
Harris, Kathleen Mullan
Tucker-Drob, Elliot M.
Waldman, Irwin D.
Palmer, Abraham A.
Harden, K. Paige
Koellinger, Philipp D.
Dick, Danielle M.

Article Type

Regular

PMCID

PMC8484054

ORCiD

Harris, KM - 0000-0001-9757-1026