Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo
| Autor: | Volker Arolt, Maurizio Fava, Willem A. Nolen, Markus M. Nöthen, Alexandra Schosser, R. van Dyck, D. H. R. Blackwood, Katharina Domschke, K. Pirlo, S.D. Gordon, Michael R. James, N. G. Martin, Wolfgang Maier, Marcella Rietschel, A. C. Heath, Yi Hu, Martin A. Kohli, Grant W. Montgomery, Susanne Lucae, Jordan W. Smoller, August B. Smit, Bernhard T. Baune, Donald J. MacIntyre, Qianchuan He, Anne Farmer, Kevin A. McGhee, Jouke-Jan Hottenga, Frans G. Zitman, Peter McGuffin, B.W.J.H. Penninx, Florian Holsboer, Dorret I. Boomsma, Patrick F. Sullivan, Jan Smit, Danielle Posthuma, Witte J.G. Hoogendijk, Danyu Lin, T. Zandbelt, Naomi R. Wray, Matthijs Verhage, Gonneke Willemsen, Jung-Ying Tzeng, Peter Heutink, E.J.C. de Geus, Walter J. Muir, Patrizia Rizzu, Roy H. Perlis, Sven Cichon, William L. Coventry |
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| Přispěvatelé: | Biological Psychology, Molecular and Cellular Neurobiology, Functional Genomics, Neuroscience Campus Amsterdam - Anxiety & Depression, Psychiatry, Human genetics, NCA - Anxiety & Depression |
| Rok vydání: | 2009 |
| Předmět: |
Male
Netherlands Twin Register (NTR) Genetic Linkage Genome-wide association study Cohort Studies NATIONAL-COMORBIDITY-SURVEY 0302 clinical medicine Copy-number variation Genetics GENERAL-POPULATION 0303 health sciences PSYCHIATRIC-DISORDERS SINGLE-NUCLEOTIDE POLYMORPHISMS Middle Aged 3. Good health FALSE DISCOVERY RATE Psychiatry and Mental health Female Psychology SAMPLE-SIZE REQUIREMENTS Presynaptic active zone Adult GENETIC-ASSOCIATION Netherlands study of depression and anxiety Single-nucleotide polymorphism Protein Piccolo COPY-NUMBER VARIATION Polymorphism Single Nucleotide Article 03 medical and health sciences Cellular and Molecular Neuroscience SDG 3 - Good Health and Well-being Humans SNP Genetic Predisposition to Disease Molecular Biology Gene 030304 developmental biology Genetic association Depressive Disorder Major SELECTION BIAS major depressive disorder Neuropeptides Netherlands twin registry Cytoskeletal Proteins HARDY-WEINBERG EQUILIBRIUM Case-Control Studies genome-wide association 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Sullivan, P F, de Geus, E J C, Willemsen, G, James, M R, Smit, J H, Zandbelt, T, Arolt, V, Baune, B T, Blackwood, D, Cichon, S, Coventry, W L, Domschke, K, Farmer, A, Fava, M, Gordon, S D, He, Q, Heath, A C, Heutink, P, Holsboer, F, Hoogendijk, W J G, Hottenga, J J, Hu, Y, Kohli, M, Lin, D, Lucae, S, MacIntyre, D J, Maier, W, McGhee, K A, McGuffin, P, Montgomery, GW, Muir, W J, Nolen, W A, Nöthen, M M, Perlis, R H, Pirlo, K, Posthuma, D, Rietschel, M, Rizzu, P, Schosser, A, Smit, A B, Smoller, J W, Tzeng, J Y, van Dyck, R, Verhage, M, Zitman, F G, Martin, N G, Wray, N R, Boomsma, D I & Penninx, B W J H 2009, ' Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo ', Molecular Psychiatry, vol. 14, no. 4, pp. 359-375 . https://doi.org/10.1038/mp.2008.125 Molecular Psychiatry, 14(4), 359-375. Nature Publishing Group Molecular psychiatry Sullivan, P F, de Geus, E J C, Willemsen, G, James, M R, Smit, J H, Zandbelt, T, Arolt, V, Baune, B T, Blackwood, D, Cichon, S, Coventry, W L, Domschke, K, Farmer, A, Fava, M, Gordon, S D, He, Q, Heath, A C, Heutink, P, Holsboer, F, Hoogendijk, W J, Hottenga, J J, Hu, Y, Kohli, M, Lin, D, Lucae, S, MacIntyre, D J, Maier, W, McGhee, K A, McGuffin, P, Montgomery, G W, Muir, W J, Nolen, W A, Noethen, M M, Perlis, R H, Pirlo, K, Posthuma, D, Rietschel, M, Rizzu, P, Schosser, A, Smit, A B, Smoller, J W, Tzeng, J-Y, van Dyck, R, Verhage, M, Zitman, F G, Martin, N G, Wray, N R, Boomsma, D I & Penninx, B W J H 2009, ' Genome-wide association for major depressive disorder : a possible role for the presynaptic protein piccolo ', Molecular Psychiatry, vol. 14, no. 4, pp. 359-375 . https://doi.org/10.1038/mp.2008.125 |
| ISSN: | 1359-4184 |
| Popis: | Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 x 10(-7) for rs2715148 and 1.2 x 10(-6) for rs2522833. We undertook replication of SNPs in this region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded P=6.4 x 10(-8) for the nonsynonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies. |
| Databáze: | OpenAIRE |
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