TY - JOUR
T1 - The genetics of antipsychotic induced tremors
T2 - a genome-wide pathway analysis on the STEP-BD SCP sample
AU - Drago, Antonio
AU - Crisafulli, Concetta
AU - Serretti, Alessandro
N1 - Copyright © 2011 Wiley Periodicals, Inc.
PY - 2011/12
Y1 - 2011/12
N2 - Extrapyramidal symptoms (EPS) are associated with antipsychotic treatment. The exact definition of the genetic variants that influence the antipsychotic induced EPS would dramatically increase the quality of antipsychotic prescriptions. We investigated this issue in a subsample of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Four hundred nine manic patients were treated with antipsychotics and had complete clinical and genetic data. Outcome was an item of the Clinical Monitoring Form which scored tremors from 0 to 4 at each clinical visit. Visits were scheduled according to clinical issues, based on a naturalistic approach. A genomic inflation factor of 1.017 resulted after genetic quality control. Single SNPs GWAS (Plink) and molecular pathway GWAS were conducted (SNP ratio test, KEGG depository). No single SNP reached GWAS significance level of association. Molecular pathways related to cell survival events and lipid synthesis were significantly associated with antipsychotic induced EPS (P = 0.0009 for Hsa04512, Hsa01031, Hsa00230, Hsa04510, Hsa03320, Hsa04930, and Hsa04115; P = 0.0019 for Hsa04020 and Hsa00561). This finding was consistent with previous GWAS studies.
AB - Extrapyramidal symptoms (EPS) are associated with antipsychotic treatment. The exact definition of the genetic variants that influence the antipsychotic induced EPS would dramatically increase the quality of antipsychotic prescriptions. We investigated this issue in a subsample of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Four hundred nine manic patients were treated with antipsychotics and had complete clinical and genetic data. Outcome was an item of the Clinical Monitoring Form which scored tremors from 0 to 4 at each clinical visit. Visits were scheduled according to clinical issues, based on a naturalistic approach. A genomic inflation factor of 1.017 resulted after genetic quality control. Single SNPs GWAS (Plink) and molecular pathway GWAS were conducted (SNP ratio test, KEGG depository). No single SNP reached GWAS significance level of association. Molecular pathways related to cell survival events and lipid synthesis were significantly associated with antipsychotic induced EPS (P = 0.0009 for Hsa04512, Hsa01031, Hsa00230, Hsa04510, Hsa03320, Hsa04930, and Hsa04115; P = 0.0019 for Hsa04020 and Hsa00561). This finding was consistent with previous GWAS studies.
KW - Adult
KW - Aged
KW - Antipsychotic Agents/adverse effects
KW - Basal Ganglia Diseases/chemically induced
KW - Bipolar Disorder/drug therapy
KW - Case-Control Studies
KW - Female
KW - Genetic Predisposition to Disease
KW - Genome
KW - Genome-Wide Association Study
KW - Humans
KW - Male
KW - Middle Aged
KW - Polymorphism, Single Nucleotide
KW - Tremor/chemically induced
U2 - 10.1002/ajmg.b.31245
DO - 10.1002/ajmg.b.31245
M3 - Journal article
C2 - 21990027
SN - 1552-4841
VL - 156B
SP - 975
EP - 986
JO - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
IS - 8
ER -