Journal
PSYCHIATRY RESEARCH
Volume 198, Issue 3, Pages 424-429Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.psychres.2012.01.023
Keywords
Pharmacogenomics; Pharmacogenetics; GWAS; Adverse drug reaction; Antidepressant; Norepinephrine
Categories
Funding
- Japan Health Sciences Foundation (Research on Publicly Essential Drugs and Medical Devices)
- Grants-in-Aid for Scientific Research [23390143] Funding Source: KAKEN
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Sexual dysfunction is a major side effect of selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs). We conducted a genome-wide association study to identify the genetic factors contributing to the risk of SSRI/SNRI-induced sexual dysfunction by testing 186 320 single nucleotide polymorphism (SNP) markers in a cohort of 201 Japanese major depression patients including 36 with sexual dysfunction induced by SSRI (paroxetine or fluvoxamine) or SNRI (milnacipran). The Cochran-Armitage trend test showed that 11 SNPs, tightly clustered in a distinct region on chromosome 14q21.3, were associated with SSRI/SNRI-induced sexual dysfunction at a genome-wide significance level after false discovery rate (FDR) correction, and the strongest SNP association was with rs1160351 (P = 3.04 x 10(-7) risk ratio = 2.92, 95% confidence interval (CI) = 1.79-4.76). These SNPs mapped to the intronic region of the MDGA2 gene. A Manhattan plot showed that the strong association peak remained in MDGA2 after adjustment for sex and age in a multivariable logistic regression analysis although P values increased slightly and became non-significant. Replication studies with larger sample sizes are required to validate this exploratory study, but our findings may provide insights into the genetic basis of sexual dysfunction induced by SSRI/SNRI. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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