Journal article
Genomewide association study of movement-related adverse antipsychotic effects
Biological psychiatry (1969), Vol.67(3), pp.279-282
02/01/2010
DOI: 10.1016/j.biopsych.2009.08.036
PMCID: PMC3388725
PMID: 19875103
Abstract
Understanding individual differences in the development of extrapyramidal side effects (EPS) as a response to antipsychotic therapy is essential to individualize treatment.
We performed genomewide association studies to search for genetic susceptibility to EPS. Our sample consisted of 738 schizophrenia patients, genotyped for 492K single nucleotide polymorphisms (SNPs). We studied three quantitative measures of antipsychotic adverse drug reactions-the Simpson-Angus Scale (SAS) for Parkinsonism, the Barnes Akathisia Rating Scale, and the Abnormal Involuntary Movement Scale (AIMS)-as well as a clinical diagnosis of probable tardive dyskinesia.
Two SNPs for SAS, rs17022444 and rs2126709 with p = 1.2 x 10(-10) and p = 3.8 x 10(-7), respectively, and one for AIMS, rs7669317 with p = 7.7 x 10(-8), reached genomewide significance (Q value < .1). rs17022444 and rs7669317 were located in intergenic regions and rs2126709 was located in ZNF202 on 11q24. Fourteen additional signals were potentially interesting (Q value < .5). The ZNF202 is a transcriptional repressor controlling, among other genes, PLP1, which is the major protein in myelin. Mutations in PLP1 cause Pelizaeus-Merzbacher disease, which has Parkinsonism as an occurring symptom. Altered mRNA expression of PLP1 is associated with schizophrenia.
Although our findings require replication and validation, this study demonstrates the potential of genomewide association studies to discover genes and pathways that mediate adverse effects of antipsychotics.
Details
- Title: Subtitle
- Genomewide association study of movement-related adverse antipsychotic effects
- Creators
- Karolina Aberg - Virginia Commonwealth University Medical CenterDaniel E Adkins - Virginia Commonwealth University Medical CenterJózsef Bukszár - Virginia Commonwealth University Medical CenterBradley T Webb - Virginia Commonwealth University Medical CenterStanley N Caroff - University of PennsylvaniaDel D Miller - Roy J. and Lucille A. Carver College of MedicineJonathan Sebat - Cold Spring Harbor LaboratoryScott Stroup - University of North Carolina at Chapel HillAyman H Fanous - Georgetown University Medical CenterVladimir I Vladimirov - Virginia Commonwealth University Medical CenterJoseph L McClay - Virginia Commonwealth University Medical CenterJeffrey A Lieberman - Columbia UniversityPatrick F Sullivan - Karolinska InstitutetEdwin J C G van den Oord - Virginia Commonwealth University Medical Center
- Resource Type
- Journal article
- Publication Details
- Biological psychiatry (1969), Vol.67(3), pp.279-282
- DOI
- 10.1016/j.biopsych.2009.08.036
- PMID
- 19875103
- PMCID
- PMC3388725
- ISSN
- 0006-3223
- eISSN
- 1873-2402
- Grant note
- HG004240 / NHGRI NIH HHS R01 MH078069 / NIMH NIH HHS MH078069 / NIMH NIH HHS MH074027 / NIMH NIH HHS N01 MH90001 / WHI NIH HHS R01 MH077139 / NIMH NIH HHS R01 MH080015 / NIMH NIH HHS MH077139 / NIMH NIH HHS R01 HG004240 / NHGRI NIH HHS R24 HD050924 / NICHD NIH HHS R01 MH074027 / NIMH NIH HHS
- Language
- English
- Date published
- 02/01/2010
- Academic Unit
- Psychiatry
- Record Identifier
- 9984280871102771
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