Genome-wide association studies of schizophrenia: does bigger lead to better results?

Abstract

Numerous genome-wide association studies (GWAS) of schizophrenia have been published in the past 6 years, with a number of key reports published in the last year. The studies have evolved in scale from small individual samples to large collaborative endeavors. This review aims to critically assess whether the results have improved as the sample size and scale of genetic association studies have grown. Genomic genotyping and increasing sample sizes for schizophrenia association studies have led to parallel increases in the number of risk genes discovered with high statistical confidence. Nearly 20 genes or loci have surpassed the genome-wide significance threshold (P = 5 × 10) in a single study, and several have been replicated in more than one GWAS. Identifying the genetic underpinnings of complex diseases offers insight into the etiological mechanisms leading to manifestation of the disease. New and more effective treatments for schizophrenia are desperately needed, and the ability to target the relevant biological processes grows with our understanding of the genes involved. As the size of GWAS samples has increased, more genes have been identified with high confidence that have begun to provide insight into the etiological and pathophysiological foundations of this disorder.