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

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

Richard Karlsson Linnér, Travis T Mallard, Peter B Barr, Sandra Sanchez-Roige, James W Madole, Morgan N Driver, Holly E Poore, Ronald de Vlaming, Andrew D Grotzinger, Jorim J Tielbeek, …
Nature neuroscience, Vol.24(10), pp.1367-1376
10/2021
DOI: 10.1038/s41593-021-00908-3
PMCID: PMC8484054
PMID: 34446935

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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.
Computational Biology Attention Deficit Disorder with Hyperactivity - genetics Behavior, Addictive - genetics Behavior, Addictive - psychology Behavioral Symptoms - genetics Behavioral Symptoms - psychology Crime - psychology Genetic Association Studies Genome-Wide Association Study HIV Infections - genetics HIV Infections - psychology Humans Meta-Analysis as Topic Multifactorial Inheritance Multivariate Analysis Opioid-Related Disorders - genetics Opioid-Related Disorders - psychology Reproducibility of Results Self-Control Suicide Unemployment

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