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

Autor: 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, Kranzler, Henry R., Gelernter, Joel, Harris, Kathleen Mullan, Tucker-Drob, Elliot M., Waldman, Irwin D., Palmer, Abraham A., Harden, K. Paige, Koellinger, Philipp D., Dick, Danielle M.
Zdroj: Nature Neuroscience; October 2021, Vol. 24 Issue: 10 p1367-1376, 10p
Abstrakt: 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.
Databáze: Supplemental Index
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