A guide on gene prioritization in studies of psychiatric disorders

Abstract

There has been an increasing interest in the identification of genetic variants causing individual differences in human behavior. Psychiatrists have contributed to the genetics field by defining the most important behavioral characteristics and by studying the association between genetic variants and behavioral differences within phenotypically well-characterized samples in which detailed assessments have been collected (e.g. neuroimaging). These samples are typically limited in size and are therefore not suitable for a genome-wide association analysis. Instead, gene association studies conducted in such samples typically focus on a few genes of interest, allowing smaller sample sizes. However, the selection of high-priority genes is not always straightforward and psychiatrists will usually have a limited background in genetics. We aim to fill this gap by (i) providing a basic introduction to genetics; (ii) showing how the selection of genes of interest can be optimized by the use of two web tools: Polysearch and Gene Prospector; (iii) illustrating how statistical power analyses can be performed and discussing the importance of sufficiently powered studies. This guide can help psychiatrists with limited experience in genetics in designing genetic studies that allow identification of specific behavioral, cognitive, or neural correlates of genetic risk variants, while avoiding common pitfalls.