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)
c1 Address for correspondence: Dr S. L. Clark, Center for Biomarker Research and Personalized Medicine, School of Pharmacy, McGuire Hall, Room 216A, P.O. Box 980533, Richmond, VA 23298-0581, USA. (Email: [email protected])