Dataset Information

Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.

ABSTRACT: BACKGROUND: Myelin transcription factor 1-like (MYT1L) is a member of the myelin transcription factor 1 (MYT1) gene family, and the neural specific, zinc-finger-containing, DNA-binding protein that it encodes plays a role in the development of the nervous system. On the basis of a recent copy number variation (CNV) study showing that this gene is disrupted in mental disorder patients, we investigated whether MYT1L also plays a role in MDD. METHODS: In this study, 8 SNPs were analyzed in 1139 MDD patients and 1140 controls of Chinese Han origin. RESULTS: Statistically significant differences were noted between cases and controls for rs3748989 (allele: permutated p = 0.0079, corrected p = 0.0048, genotype: corrected p?=?0.0204). A haplotype of rs1617213 and rs6759709 G-C was also significant (permutated p = 0.00007). CONCLUSION: Our results indicate that MYT1L may be a potential risk gene for MDD in the Chinese Han population.

SUBMITTER: Wang T

PROVIDER: S-EPMC2965102 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.

Wang Ti T Zeng Zhen Z Li Tao T Liu Jie J Li Junyan J Li You Y Zhao Qian Q Wei Zhiyun Z Wang Yang Y Li Baojie B Feng Guoyin G He Lin L Shi Yongyong Y

PloS one 20101027 10

<h4>Background</h4>Myelin transcription factor 1-like (MYT1L) is a member of the myelin transcription factor 1 (MYT1) gene family, and the neural specific, zinc-finger-containing, DNA-binding protein that it encodes plays a role in the development of the nervous system. On the basis of a recent copy number variation (CNV) study showing that this gene is disrupted in mental disorder patients, we investigated whether MYT1L also plays a role in MDD.<h4>Methods</h4>In this study, 8 SNPs were analyze ...[more]

PMID: 21048971

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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:The D2 dopamine receptor (DRD2) has been extensively investigated and has been associated with the occurrence of neuropsychiatric disorders. Polymorphisms in the DRD2 gene have also been determined as a possible predisposing component for major depressive disorders (MDD). The present study focused on evaluating the connection of polymorphisms inside the whole DRD2 gene in MDD patients as well as in non-MDD participants in a group selected from the Chinese Han population. MATERIALS AND METHODS:In total, 831 unrelated Chinese adults from the Han population were sampled, including 497 non-MDD participants and 334 MDD patients for this evaluation. After the haplotype bins were built, 14 tag single-nucleotide polymorphisms (tSNPs) and the two most investigated SNP were chosen for the whole DRD2 gene. An improved multiplex ligation detection reaction (iMLDR) technique was used to choose the genotypes. Following this, the allelic frequencies and clinical features were contrasted between the two independent Chinese Han populations. Transcriptional enhancer activities were measured to assess the functionality of the rs7131056 polymorphism. RESULTS:Sixteen SNPs were identified, including the two most examined in the Chinese Han population, and all were recurrent SNPs. Of the 16 SNPs, two (rs4648317 and rs7131056) were significantly connected to MDD. Patients with MDD were more apt to carry the rs4648317G and rs7131056A allele in contrast to the non-MDD controls (P < 0.05). The genetic risk effect on MDD occurrence was associated with the haplotype GTGATCGCGCAGGC of fourteen tag SNPs (OR = 1.52, 95% CI: 1.06 to 2.18, P = 0.02). Moreover, the rs7131056 polymorphism contained intronic silencer activities. CONCLUSIONS:This case-control evaluation involving the Chinese Han population suggests that the rs4648317 and rs7131056 polymorphisms and the haplotype GTGATCGCGCAGGC inside the DRD2 gene could be possible markers to forecast vulnerability to MDD.

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 SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.

Publications

Common SNPs in myelin transcription factor 1-like (MYT1L): association with major depressive disorder in the Chinese Han population.

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