title: Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway.
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.
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Cocchi
authors.affiliation: Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Chiara
authors.initials: C
authors.lastname: Fabbri
authors.affiliation: Department of Psychiatry, Korea University, College of Medicine, Seoul, Republic of Korea.
authors.forename: Changsu
authors.initials: C
authors.lastname: Han
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea.
authors.forename: Soo-Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA.
authors.forename: Ashwin A
authors.initials: AA
authors.lastname: Patkar
authors.affiliation: Global Medical Education, New York, NY, USA.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Masand
authors.affiliation: Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, Republic of Korea. pae@catholic.ac.kr.|Department of Psychiatry and Behavioural Sciences, Duke University Medical Center, Durham, NC, USA. pae@catholic.ac.kr.
authors.forename: Chi-Un
authors.initials: CU
authors.lastname: Pae
authors.affiliation: Department of Biomedical and NeuroMotor Sciences, University of Bologna, Bologna, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Serretti
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D000928:Antidepressive Agents; D027701:Organic Cation Transport Proteins
keywords: Antidepressant; Calcium channel; Cation transmembrane transporter; GWAS; Gene; Major depression; Pathway; Pharmacogenomics