The genetics of antipsychotic induced tremors: A genome-wide pathway analysis on the STEP-BD SCP sample

Antonio Drago, Concetta Crisafulli, Alessandro Serretti

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)975-986
Number of pages12
JournalAmerican Journal of Medical Genetics - Neuropsychiatric Genetics
Volume156
Issue number8
DOIs
Publication statusPublished - Dec 2011

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Keywords

  • Antipsychotic
  • Extrapyramidal symptom
  • GWAS
  • Pathway analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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