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

Karlsson Linner, R.; Mallard, T. T.; Barr, P. B.; Sanchez-Roige, S.; Madole, J. W.; Driver, M. N.; Poore, H. E.; Grotzinger, A. D.; Tielbeek, J. J.; Johnson, E. C.; Liu, M.; Zhou, H.; Kember, R.; Pasman, J. A.; Verweij, K. J. H.; Liu, D.; Vrieze, S.; Kranzler, H.; Gelernter, J.; Mullan Harris, K.; Tucker-Drob, E. M.; Waldman, I. D.; Palmer, A. A.; Harden, K. P.; Koellinger, P. D.; Dick, D. M.

doi:10.1101/2020.10.16.342501

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bioRxiv · 10.1101/2020.10.16.342501

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

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Abstract

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. 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 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. Our findings are consistent with the idea that persistent difficulties in self-regulation can be conceptualized as a neurodevelopmental condition.

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Karlsson Linner, R., Mallard, T. T., Barr, P. B., Sanchez-Roige, S., Madole, J. W., Driver, M. N., Poore, H. E., Grotzinger, A. D., Tielbeek, J. J., Johnson, E. C., Liu, M., Zhou, H., Kember, R., Pasman, J. A., Verweij, K. J. H., Liu, D., Vrieze, S., Kranzler, H., Gelernter, J., Mullan Harris, K., Tucker-Drob, E. M., Waldman, I. D., Palmer, A. A., Harden, K. P., Koellinger, P. D., Dick, D. M.. 2020-10-16. Multivariate genomic analysis of 1.5 million people identifies genes related to addiction, antisocial behavior, and health. https://doi.org/10.1101/2020.10.16.342501

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