Genetic Studies of Mental Illness: Are Children Being Left Behind?

Abstract

Understanding the genetic architecture of psychiatric disorders is paramount to linking psychopathologies to their genetic underpinnings. In turn, this knowledge can inform strategies for identifying high-risk individuals, early intervention, and development of personalized treatment approaches.^1,2 Over the past 2 decades, owing to lowering per capita costs and relative ease of analysis, a plethora of studies have used single nucleotide polymorphism genotyping and genome-wide association studies (GWASs) to unravel common and rare risk loci underlying psychiatric disorders and their endophenotypes.³ In contrast to the single allele focus of classical Mendelian inheritance, mental illnesses are often polygenic in nature with multiple common genetic variants, each contributing a small, but meaningful added risk. By interrogating the entire genome, GWASs have allowed the functional assessment of promising candidate genes in in vivo as well as in vitro models of psychiatric disease. Further, these findings have spawned the approach of calculating polygenic risk scores, a promising strategy for inferring genetic susceptibility to the development of psychopathology by taking into account the polygenic structure of psychiatric disorders.