Genome-wide association study of antidepressant response: involvement of the inorganic cation transmembrane transporter activity pathway
Year: 2016
Type: article
Study design: Observational Study
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.
Source: BMC Psychiatry
Authors: Enrico Cocchi, Chiara Fabbri, Changsu Han, Soo-Jung Lee, Ashwin A. Patkar, Prakash S. Masand, Chi-Un Pae, Alessandro Serretti
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,290
Funders: Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Sunovion, Jazz Pharmaceuticals, BioDelivery Sciences International, Eisai, Servier, H. Lundbeck A/S, Dong Wha Pharm, Italfarmaco, National Institutes of Health, Substance Abuse and Mental Health Services Administration, Eisai Korea, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Institute on Drug Abuse, Daiichi Sankyo Europe
OpenAlex ID: W2336419809