Dataset Information

Targeted sequencing of the BDNF gene in young Chinese Han people with major depressive disorder.

ABSTRACT: BACKGROUND:Adolescence and young adulthood are considered the peak age for the emergence of many psychiatric disorders, in particular major depressive disorder (MDD). Previous research has shown substantial heritability for MDD. In addition, the brain-derived neurotrophic factor (BDNF) gene is known to be associated with MDD. However, there has been no study conducting targeted sequencing of the BDNF gene in young MDD patients so far. METHOD:To examine whether the BDNF gene is associated with the occurrence of MDD in young patients, we used targeted sequencing to detect the BDNF gene variants in 259 young Chinese Han people (105 MDD patients and 154 healthy subjects). RESULTS:The BDNF variant rs4030470 was associated with MDD in young Chinese Han people (uncorrected p = 0.046), but this was no longer significant after applying FDR correction (p = 0.552, after FDR correction). We did not find any significant differences in genotype or haplotype frequencies between the case and control groups, and furthermore discovered no rare mutation variants any of the 259 subjects. CONCLUSION:Our results do not support an association of the BDNF gene variants with MDD in young people in the Chinese Han population.

SUBMITTER: Zhang C

PROVIDER: S-EPMC7549566 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Targeted sequencing of the BDNF gene in young Chinese Han people with major depressive disorder.

Zhang Chenyu C Ran Liuyi L Ai Ming M Wang Wo W Chen Jianmei J Wu Tong T Liu Wei W Jin Jiajia J Wang Suya S Kuang Li L

Molecular genetics & genomic medicine 20200831 10

<h4>Background</h4>Adolescence and young adulthood are considered the peak age for the emergence of many psychiatric disorders, in particular major depressive disorder (MDD). Previous research has shown substantial heritability for MDD. In addition, the brain-derived neurotrophic factor (BDNF) gene is known to be associated with MDD. However, there has been no study conducting targeted sequencing of the BDNF gene in young MDD patients so far.<h4>Method</h4>To examine whether the BDNF gene is ass ...[more]

PMID: 32869548

Similar Datasets

Project description:ImportanceDespite the moderate, well-demonstrated heritability of major depressive disorder (MDD), there has been limited success in identifying replicable genetic risk loci, suggesting a complex genetic architecture. Research is needed to quantify the relative contribution of classes of genetic variation across the genome to inform future genetic studies of MDD.ObjectivesTo apply aggregate genetic risk methods to clarify the genetic architecture of MDD by estimating and partitioning heritability by chromosome, minor allele frequency, and functional annotations and to test for enrichment of rare deleterious variants.Design, setting, and participantsThe CONVERGE (China, Oxford, and Virginia Commonwealth University Experimental Research on Genetic Epidemiology) study collected data on 5278 patients with recurrent MDD from 58 provincial mental health centers and psychiatric departments of general medical hospitals in 45 cities and 23 provinces of China. Screened controls (n = 5196) were recruited from a range of locations, including general hospitals and local community centers. Data were collected from August 1, 2008, to October 31, 2012.Main outcomes and measuresGenetic risk for liability to recurrent MDD was partitioned using sparse whole-genome sequencing.ResultsIn aggregate, common single-nucleotide polymorphisms (SNPs) explained between 20% and 29% of the variance in MDD risk, and the heritability in MDD explained by each chromosome was proportional to its length (r = 0.680; P = .0003), supporting a common polygenic etiology. Partitioning heritability by minor allele frequency indicated that the variance explained was distributed across the allelic frequency spectrum, although relatively common SNPs accounted for a disproportionate fraction of risk. Partitioning by genic annotation indicated a greater contribution of SNPs in protein-coding regions and within 3'-UTR regions of genes. Enrichment of SNPs associated with DNase I-hypersensitive sites was also found in many tissue types, including brain tissue. Examining burden scores from singleton exonic SNPs predicted to be deleterious indicated that cases had significantly more mutations than controls (odds ratio, 1.009; 95% CI, 1.003-1.014; P = .003), including those occurring in genes expressed in the brain (odds ratio, 1.011; 95% CI, 1.003-1.018; P = .004) and within nuclear-encoded genes with mitochondrial gene products (odds ratio, 1.075; 95% CI, 1.018-1.135; P = .009).Conclusions and relevanceResults support a complex etiology for MDD and highlight the value of analyzing components of heritability to clarify genetic architecture.

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

Targeted sequencing of the BDNF gene in young Chinese Han people with major depressive disorder.

Publications

Targeted sequencing of the BDNF gene in young Chinese Han people with major depressive disorder.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets