@article{d5056cc9738a4e4b9878a3ec1602cf3f,
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.",
keywords = "Antidepressant, Calcium channel, Cation transmembrane transporter, GWAS, Gene, Major depression, Pathway, Pharmacogenomics",
author = "Enrico Cocchi and Chiara Fabbri and Changsu Han and Lee, {Soo Jung} and Patkar, {Ashwin A.} and Masand, {Prakash S.} and Pae, {Chi Un} and Alessandro Serretti",
note = "Funding Information: Data and biomaterials were obtained from the limited access datasets distributed from the NIH-supported “Sequenced Treatment Alternatives to Relieve Depression” (STAR*D). STAR*D focused on non-psychotic major depressive disorder in adults seen in outpatient settings. The primary purpose of this research study was to determine which treatments work best if the first treatment with medication does not produce an acceptable response. The study was supported by NIMH Contract # N01MH90003 to the University of Texas Southwestern Medical Center. The ClinicalTrials.gov identifier is NCT00021528. Funding Information: This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0003). The authors are solely responsible for the content of the manuscript and the decision to submit for publication. Funding Information: AS is or has been consultant/speaker for: Abbott, Abbvie, Angelini, Astra Zeneca, Clinical Data, Boheringer, Bristol Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polipharma, Sanofi, Servier. PSM is or has been consultant/speaker for: Actavis, Forest, Merck, Glaxo Smith Kline, Lundbeck, Merck, Pamlabs, Pfizer, Sunovion, and Takeda; has received Research Support from Actavis, and has stock ownership for Global Medical Education. AAP is a Consultant/Advisory Board for Cubist Pharma; BDSI, Titan Pharma, Kaleo Pharma, is on the Speaker{\textquoteright}s Bureau and received honoraria from Otsuka, Alkermes, Sunovion and BDSI; has received Grant Support from National Institutes of Health (NIDA, NIAAA), SAMHSA, AstraZeneca, Bristol-Myers Squibb, Cephalon, Daiichi Sankyo, Envivo Pharma, Forest, J & J, Jazz Pharmaceuticals, Lundbeck, Merck, Organon, Pfizer, Sunovion, Shire and Titan; is a major shareholder in Generys Biopharmaceuticals, and is not employed by or received other material support from pharmaceutical companies. CUP has been consultant/speaker for: Pfizer Korea, Lundbeck Korea, Sandoz Korea, OIAA, Otsuka Korea, Otsuka Japan, Daiichisankyo, GSK Korea; has received research grants from OIAA, Otsuka Korea, Eisai Korea, Korean Research Foundation, and Korean Ministry of Health and Welfare. CH has been consultant/speaker for: Pfizer Korea, Lundbeck Korea, Sandoz Korea, OIAA, Otsuka Korea, Otsuka Japan, Otsuka Turkey, Dongwha pharmaceuticals, GSK Korea; has received research grants from OIAA, Otsuka Korea, Eisai Korea, Korean Research Foundation, and Korean Ministry of Health and Welfare. Remaining authors do not have competing interests to report. Publisher Copyright: {\textcopyright} 2016 Cocchi et al.",
year = "2016",
month = apr,
day = "18",
doi = "10.1186/s12888-016-0813-x",
language = "English",
volume = "16",
journal = "BMC Psychiatry",
issn = "1471-244X",
publisher = "BioMed Central",
number = "1",
}