Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort
| Autor: | Marianna R. Bevova, Zoltán Bochdanovits, Tiny Uithuisje, Johannes H. Smit, I. Bakker, Eva C. Verbeek, Patrizia Rizzu, Eco J. C. de Geus, Brenda W.J.H. Penninx, Dorret I. Boomsma, Witte J.G. Hoogendijk, Peter Heutink |
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| Přispěvatelé: | Functional Genomics, Biological Psychology, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Neuroscience Campus Amsterdam - Brain Imaging Technology, Clinical Genetics, Psychiatry, Human genetics, Epidemiology and Data Science, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, EMGO - Mental health, NCA - Brain imaging technology |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Netherlands Twin Register (NTR)
Linkage disequilibrium Candidate gene lcsh:Medicine Single-nucleotide polymorphism Genome-wide association study Biology Receptors Metabotropic Glutamate Polymorphism Single Nucleotide Cohort Studies 03 medical and health sciences 0302 clinical medicine SDG 3 - Good Health and Well-being mental disorders SNP Humans lcsh:Science Promoter Regions Genetic 030304 developmental biology Genetic association Netherlands Genetics Serotonin Plasma Membrane Transport Proteins 0303 health sciences Depressive Disorder Major Multidisciplinary lcsh:R Neuropeptides Epistasis Genetic Cytoskeletal Proteins Haplotypes Cohort lcsh:Q 030217 neurology & neurosurgery Imputation (genetics) Research Article Genome-Wide Association Study |
| Zdroj: | PLoS ONE Verbeek, E C, Bevova, M R, Bochdanovits, Z, Rizzu, P, Bakker, I M C, Uithuisje, T, de Geus, E J C, Smit, J H, Penninx, B W J H, Boomsma, D I, Hoogendijk, W J G & Heutink, P 2013, ' Resequencing Three Candidate Genes for Major Depressive Disorder in a Dutch Cohort ', PLoS ONE, vol. 8, no. 11, e79921, pp. e79921 . https://doi.org/10.1371/journal.pone.0079921 PLoS ONE, 8(11):e79921. Public Library of Science PLoS One (print), 8(11):e79921. Public Library of Science PLoS ONE, Vol 8, Iss 11, p e79921 (2013) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0079921 |
| Popis: | Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort. © 2013 Verbeek et al. |
| Databáze: | OpenAIRE |
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