Colloquium - Genetic Associations with Externalizing Behaviors in Nearly 4 Million People

Abstract:
 A child hits other children on the playground and disobeys their teacher. An adolescent tries drugs and vandalizes a neighbor’s home. An adult abuses alcohol and cheats on their taxes. All these behaviors are part of what psychiatrists have labeled the “externalizing” spectrum, which is characterized by persistent problems with disinhibition (impulsivity without regard to future negative consequences) and antagonism (callousness to or disregard of the needs of others). Externalizing problems onset early in life, often before school-age, and commonly persist throughout midlife. These problems are extremely costly to individual well-being and to society. But despite this public health burden, the development of effective treatments has been slow. Because externalizing behaviors are highly heritable, genetic studies have the potential to illuminate biopsychosocial mechanisms for the development of externalizing disorders and suggest new targets for effective treatment. In this presentation, I will describe results from a multivariate genome-wide association study of 7 externalizing behaviors in nearly 4 million individuals whose genomes are most similar to reference panels from Europe (“EUR-like”, N ~ 3.8 million) and Africa (“AFR-like”, N ~ 250,000). We identify more than 1,400 genome-wide significant risk loci, and a resulting polygenic index (PGI) captures meaningful variance in externalizing outcomes and physical health conditions across development, with minimal attenuation in within-family comparisons. I conclude by considering some of the ethical implications of genetic research on moralized and socially disciplined behaviors.