Genome-wide association studies of antidepressant outcome: a brief review

Genome-wide association studies (GWAS) of antidepressant treatment outcome have been at the forefront of psychiatric pharmacogenetics. Such studies may ultimately help match medications with patients, maximizing efficacy while minimizing adverse effects. The hypothesis-free approach of the GWAS has the advantage of interrogating genes that otherwise would have not been considered as candidates due to our limited understanding of their function, and may also uncover important regulatory variation within the large regions of the genome that do not contain protein-coding genes. Three independent samples have so far been studied using a genome-wide approach: The Sequenced Treatment Alternatives to Relieve Depression sample (STAR*D) (n = 1953), the Munich Antidepressant Response Signature (MARS) sample (n = 339) and the Genome-based Therapeutic Drugs for Depression (GENDEP) sample (n = 706). None of the studies reported results that achieved genome-wide significance, suggesting that larger samples and better outcome measures will be needed. This review discusses the published GWAS studies, their strengths, limitations, and possible future directions.