Psychological Medicine

Original Articles

Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D

S. L. Clarka1 c1, D. E. Adkinsa1, K. Aberga1, J. M. Hettemaa2, J. L. McClaya1, R. P. Souzaa3 and E. J. C. G. van den Oorda1

a1 Center for Biomarker Research and Personalized Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA

a2 Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA

a3 Laboratory of Neurosciences, Universidade Do Extremo Sul Catarinense, Criciuma, SC, Brazil


Background Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.

Method We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.

Results Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p=4.98×10−7, q=0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1.

Conclusions Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.

(Received June 07 2011)

(Revised September 08 2011)

(Accepted September 14 2011)

(Online publication November 01 2011)