title: Genome-wide association study of SSRI/SNRI-induced sexual dysfunction in a Japanese cohort with major depression.
abstract: 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 × 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.
authors.affiliation: Division of Medicinal Safety Science, National Institute of Health Sciences, Tokyo, Japan. kurose@nihs.go.jp
authors.forename: Kouichi
authors.initials: K
authors.lastname: Kurose
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Hiratsuka
authors.forename: Kazuya
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Jun
authors.initials: J
authors.lastname: Nishikawa
authors.forename: Shinpei
authors.initials: S
authors.lastname: Nonen
authors.forename: Junichi
authors.initials: J
authors.lastname: Azuma
authors.forename: Masaki
authors.initials: M
authors.lastname: Kato
authors.forename: Masataka
authors.initials: M
authors.lastname: Wakeno
authors.forename: Gaku
authors.initials: G
authors.lastname: Okugawa
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Toru
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hasegawa
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Saito
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics / Q000523:psychology; D015331:Cohort Studies; D003521:Cyclopropanes / Q000009:adverse effects*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy; D005260:Female; D016666:Fluvoxamine / Q000009:adverse effects*; D058851:GPI-Linked Proteins / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000706:statistics & numerical data*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D000078764:Milnacipran; D019006:Neural Cell Adhesion Molecules / Q000235:genetics*; D017374:Paroxetine / Q000009:adverse effects*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced*; D020018:Sexual Dysfunctions, Psychological / Q000150:complications / Q000235:genetics*
chemical_list: D018759:Adrenergic Uptake Inhibitors; D003521:Cyclopropanes; D016666:Fluvoxamine; D058851:GPI-Linked Proteins; D000078764:Milnacipran; D019006:Neural Cell Adhesion Molecules; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; C544522:MDGA2 protein, human