Dataset Information

Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.

ABSTRACT: Accumulating evidence suggests that genetic factors have a role in major depressive disorder (MDD). However, only limited MDD risk loci have been identified so far. Here we perform a meta-analysis (a total of 90,150 MDD cases and 246,603 controls) through combing three genome-wide association studies of MDD, including 23andMe (cases were self-reported with a clinical diagnosis or treatment of depression), CONVERGE (cases were diagnosed using the Composite International Diagnostic Interview) and PGC (cases were diagnosed using direct structured diagnostic interview (by trained interviewers) or clinician-administered DSM-IV checklists). Genetic variants from two previously unreported loci (rs10457592 on 6q16.2 and rs2004910 on 12q24.31) showed significant associations with MDD (P?

SUBMITTER: Li X

PROVIDER: S-EPMC6098070 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Publications

Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.

Li Xiaoyan X Luo Zhenwu Z Gu Chunjie C Hall Lynsey S LS McIntosh Andrew M AM Zeng Yanni Y Porteous David J DJ Hayward Caroline C Li Ming M Yao Yong-Gang YG Zhang Chen C Luo Xiong-Jian XJ

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20180427 10

Accumulating evidence suggests that genetic factors have a role in major depressive disorder (MDD). However, only limited MDD risk loci have been identified so far. Here we perform a meta-analysis (a total of 90,150 MDD cases and 246,603 controls) through combing three genome-wide association studies of MDD, including 23andMe (cases were self-reported with a clinical diagnosis or treatment of depression), CONVERGE (cases were diagnosed using the Composite International Diagnostic Interview) and ...[more]

PMID: 29728651

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Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Dataset Information

Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.

Publications

Common variants on 6q16.2, 12q24.31 and 16p13.3 are associated with major depressive disorder.

Similar Datasets

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