“Multivariate Genomic Analysis of 1.5 Million People Identifies Genes Related to Addiction, Antisocial Behavior, and Health”, Richard Karlsson Linnér, Travis T. Mallard, Peter B. Barr, Sandra Sanchez-Roige, James W. Madole, Morgan N. Driver, Holly E. Poore, Andrew D. Grotzinger, Jorim J. Tielbeek, Emma C. Johnson, Mengzhen Liu, Hang Zhou, Rachel L. Kember, Joëlle A. Pasman, Karin J. H. Verweij, Dajiang J. Liu, Scott Vrieze, COGA Collaborators, Henry R. Kranzler, Joel Gelernter, Kathleen Mullan Harris, Elliot M. Tucker-Drob, Irwin Waldman, Abraham Palmer, K. Paige Harden, Philipp Koellinger, Danielle M. Dick2020-10-16 (, , ; similar)⁠:

Behaviors and disorders related to self-regulation, such as substance use, antisocial conduct, and ADHD, are collectively referred to as externalizing and have a shared genetic liability. This comprehensive background lays the groundwork for understanding the interconnectedness of various externalizing conditions and their genetic underpinnings.

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. This methodology underscores the power of large-scale data and multivariate analysis in identifying the genetic basis of complex traits.

The identified loci were enriched for genes expressed in the brain and related to nervous system development. A polygenic score constructed from our results captures variation in a broad range of behavioral and medical outcomes that were not part of our 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. These results indicate significant progress in understanding and predicting a range of behaviors and conditions linked to externalizing traits.

Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental condition. This conclusion suggests a paradigm shift in how these behaviors and disorders are viewed, emphasizing the importance of early intervention and holistic approaches to treatment and prevention.