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

A Schosser, D Gaysina, S Cohen-Woods, E Domenici, J Perry, F Tozzi, A Korszun, C Gunasinghe, Joanna Gray, L Jones, E B Binder, F Holsboer, N Craddock, M J Owen, I W Craig, A E Farmer, P Muglia, P McGuffin

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)640 - 650
Number of pages11
JournalAmerican Journal of Medical Genetics. Part B: Neuropsychiatric Genetics
Volume156B
Issue number6
Early online date31 May 2011
DOIs
Publication statusPublished - Sept 2011

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Depressive Disorder, Major/genetics
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Germany
  • High-Throughput Screening Assays
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide Synthase Type II/genetics
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Recurrence
  • United Kingdom

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