A follow-up case-control association study of tractable (druggable) genes in recurrent major depression

Schosser, A., Gaysina, D., Cohen-Woods, S., Domenici, E., Perry, J., Tozzi, F., Korszun, A., Gunasinghe, C., Gray, J., Jones, L., Binder, E. B., Holsboer, F., Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Craig, I. W., Farmer, A. E., Muglia, P. and McGuffin, P. 2011. A follow-up case-control association study of tractable (druggable) genes in recurrent major depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 156 (6) , pp. 640-650. 10.1002/ajmg.b.31204

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Abstract

The High-Throughput Disease-specific target Identification Program (HiTDIP) aimed to study case–control association samples for 18 common diseases. Here we present the results of a follow-up case–control association study of HiTDIP in major depressive disorder (MDD). The HiTDIP in MDD was conducted in a sample of 974 cases of recurrent MDD of white German origin collected at the Max-Planck Institute (MP-GSK) and 968 ethnically matched controls screened for lifetime absence of depression. Six genes were identified as of interest for a follow-up, based on the strength of the association and based on the interest as potential candidate target for developing new treatment for depression: Solute Carrier Family 4 Member 10 (SLC4A10), Dipeptidyl Peptidase IV (DPP4), Dopamine Receptor D3 (DRD3), Zinc Finger Protein 80 (ZNF80), Nitric Oxide Synthase 2A (NOS2A) and Peroxisome Proliferator-Activated Receptor-Gamma, Coactivator 1, Alpha (PPARGC1A). Within the current study, we attempted to follow-up these findings in a sample from the UK, the Depression Case Control (DeCC) sample consisting of 1,196 cases and 842 screened controls, phenotyped using exactly the same methods as the MP-GSK sample. Performing Cochran–Mantel–Haenzel statistics to test for genotypic and/or allelic differences between the DeCC and MP-GSK samples, we found no significant differences, thus being able to combine the two samples for association testing. In the combined sample of 2,170 MDD cases and 1,810 controls, there were positive findings in the Nitric Oxide Synthase 2A (NOS2A) gene both using single SNP analysis and haplotype analysis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	depression; genetics; association; candidate genes; case–control study
Publisher:	Wiley-Blackwell
ISSN:	1552-4841
Last Modified:	19 Oct 2022 09:47
URI:	https://orca.cardiff.ac.uk/id/eprint/22216

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