title: Fine-mapping of antipsychotic response genome-wide association studies reveals novel regulatory mechanisms.
abstract: OBJECTIVE
  Noncoding variation has demonstrated regulatory effects on disease treatment outcomes. This study investigated the potential functionality of previously implicated noncoding variants on schizophrenia treatment response.
  
  
  METHODS
  Predicted regulatory potential of variation identified from antipsychotic response genome-wide association studies was determined. Prioritized variants were assessed for association(s) with treatment outcomes in a South African first episode schizophrenia cohort (n = 103).
  
  
  RESULTS
  Bioinformatic and association results implicated a relationship between regulatory variants, expression of MANBA, COL9A2 and NFKB1, and treatment response. Three SNPs were associated with poor outcomes (rs230493: p = 1.88 × 10-6; rs3774959: p = 1.75 × 10-5; and rs230504: p = 1.48 × 10-4).
  
  
  CONCLUSIONS
  This study has thoroughly investigated previous GWAS to pinpoint variants that may play a causal role in poor schizophrenia treatment outcomes, and provides potential candidate genes for further study in the field of antipsychotic response.
authors.affiliation: Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Ellen S
authors.initials: ES
authors.lastname: Ovenden
authors.affiliation: Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Britt I
authors.initials: BI
authors.lastname: Drögemöller
authors.affiliation: Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Lize
authors.initials: L
authors.lastname: van der Merwe
authors.affiliation: Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Bonginkosi
authors.initials: B
authors.lastname: Chiliza
authors.affiliation: Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Laila
authors.initials: L
authors.lastname: Asmal
authors.affiliation: Department of Psychiatry, Stellenbosch University, Tygerberg, South Africa.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Emsley
authors.affiliation: Department of Genetics, Stellenbosch University, Stellenbosch, South Africa.
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D002874:Chromosome Mapping / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D005475:Flupenthixol / Q000031:analogs & derivatives / Q000627:therapeutic use; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D013019:South Africa / Q000453:epidemiology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C007761:flupenthixol decanoate; D005475:Flupenthixol
keywords: COL9A2; ENCODE; MANBA; NFKB1; antipsychotic treatment response; flupenthixol decanoate; rSNPs; schizophrenia