All authors report no conflicts of interest.
Article first published online: 9 MAY 2012
Copyright © 2012 Wiley Periodicals, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 159B, Issue 5, pages 519–528, July 2012
How to Cite
van Veen, T., Goeman, J. J., Monajemi, R., Wardenaar, K. J., Hartman, C. A., Snieder, H., Nolte, I. M., Penninx, B. W.J.H. and Zitman, F. G. (2012), Different gene sets contribute to different symptom dimensions of depression and anxiety. Am. J. Med. Genet., 159B: 519–528. doi: 10.1002/ajmg.b.32058
How to Cite this Article: van Veen T, Goeman JJ, Monajemi R, Wardenaar KJ, Hartman CA, Snieder H, Nolte IM, Penninx BWJH, Zitman FG. 2012. Different Gene Sets Contribute to Different Symptom Dimensions of Depression and Anxiety. Am J Med Genet Part B 159B:519–528.
- Issue published online: 5 JUN 2012
- Article first published online: 9 MAY 2012
- Manuscript Accepted: 19 APR 2012
- Manuscript Received: 12 JAN 2012
- Netherlands Organisation for Health Research and Development (ZonMw). Grant Number: 10-000-1002
- tripartite model;
Although many genetic association studies have been carried out, it remains unclear which genes contribute to depression. This may be due to heterogeneity of the DSM-IV category of depression. Specific symptom-dimensions provide a more homogenous phenotype. Furthermore, as effects of individual genes are small, analysis of genetic data at the pathway-level provides more power to detect associations and yield valuable biological insight. In 1,398 individuals with a Major Depressive Disorder, the symptom dimensions of the tripartite model of anxiety and depression, General Distress, Anhedonic Depression, and Anxious Arousal, were measured with the Mood and Anxiety Symptoms Questionnaire (30-item Dutch adaptation; MASQ-D30). Association of these symptom dimensions with candidate gene sets and gene sets from two public pathway databases was tested using the Global test. One pathway was associated with General Distress, and concerned molecules expressed in the endoplasmatic reticulum lumen. Seven pathways were associated with Anhedonic Depression. Important themes were neurodevelopment, neurodegeneration, and cytoskeleton. Furthermore, three gene sets associated with Anxious Arousal regarded development, morphology, and genetic recombination. The individual pathways explained up to 1.7% of the variance. These data demonstrate mechanisms that influence the specific dimensions. Moreover, they show the value of using dimensional phenotypes on one hand and gene sets on the other hand. © 2012 Wiley Periodicals, Inc.