Multivariate genomic analysis of 1.5 million people identifies genes related to addiction, antisocial behavior, and health

Authors: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,Henry R. Kranzler,Joel Gelernter,Kathleen Mullan Harris,Elliot M. Tucker‐Drob,Irwin D. Waldman,Abraham A. Palmer,K. Paige Harden,Philipp Koellinger,Danielle M. Dick

DPID: 1055Published: 2025

Abstract

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

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