title: Pharmacogenomic study of side-effects for antidepressant treatment options in STAR*D.
abstract: BACKGROUND
  Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.
  
  
  METHODS
  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.
authors: Center for Biomarker Research and Personalized Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0581, USA. slclark2@vcu.edu
authors: S L
authors: SL
authors: Clark
authors: D E
authors: DE
authors: Adkins
authors: K
authors: K
authors: Aberg
authors: J M
authors: JM
authors: Hettema
authors: J L
authors: JL
authors: McClay
authors: R P
authors: RP
authors: Souza
authors: E J C G
authors: EJ
authors: van den Oord
mesh_terms: D000928:Antidepressive Agents / Q000009:adverse effects*; D016642:Bupropion / Q000009:adverse effects; D015283:Citalopram / Q000009:adverse effects; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000145:classification / Q000235:genetics*; D005163:Factor Analysis, Statistical; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012735:Sexual Dysfunction, Physiological / Q000139:chemically induced / Q000235:genetics; D016896:Treatment Outcome; D010744:Phosphoric Monoester Hydrolases
chemical_list: D000928:Antidepressive Agents; D016642:Bupropion; D015283:Citalopram; D008565:Membrane Proteins; C431702:SACM1L protein, human; D010744:Phosphoric Monoester Hydrolases