Genome-wide association study of antidepressant response: Involvement of the inorganic cation transmembrane transporter activity pathway

Enrico Cocchi, Chiara Fabbri, Changsu Han, Soo Jung Lee, Ashwin A. Patkar, Prakash S. Masand, Chi Un Pae, Alessandro Serretti

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Genome-wide association studies (GWAS) represent the current frontier in pharmacogenomics. Thousands of subjects of Caucasian ancestry have been included in previous GWAS investigating antidepressant response. GWAS focused on this phenotype are lacking in Asian populations. Methods: A sample of 109 major depressive disorder (MDD) patients of Korean origin in antidepressant treatment was collected. Phenotypes were response and remission according to the Hamilton Rating Scale for Depression (HRSD). Genome-wide genotyping was performed using the Illumina Human Omni2.5-8 platform. The same phenotypes were used in the STAR*D level 1 (n = 1677) for independent replication. In order to corroborate findings and increase the comparability between the two datasets, three levels of analysis (SNPs, genes and pathways) were carried out. Bonferroni correction, permutations, and replication across samples were used to reduce the risk of false positives. Results: Among the genes replicated across the two samples (permutated p < 0.05 in both of them), CTNNA3 appeared promising. The inorganic cation transmembrane transporter activity pathway (GO:0022890) was associated with antidepressant response in both samples (p = 2.9e-5 and p = 0.001 in the Korean and STAR*D samples, respectively) and this pathway included CACNA1A, CACNA1C, and CACNB2 genes. Conclusions: The present study supported the involvement of genes coding for subunits of L-type voltage-gated calcium channel in antidepressant efficacy across different ethnicities but replication of findings is required before any definitive statement.

Original languageEnglish
Article number106
JournalBMC Psychiatry
Volume16
Issue number1
DOIs
Publication statusPublished - 2016 Apr 18

Keywords

  • Antidepressant
  • Calcium channel
  • Cation transmembrane transporter
  • GWAS
  • Gene
  • Major depression
  • Pathway
  • Pharmacogenomics

ASJC Scopus subject areas

  • Psychiatry and Mental health

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