Rare Gene Variant Linked To Depressive Symptoms

MedicalResearch.com Interview with:
Najaf Amin, PhD
Erasmus University Medical Center

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Identifying genetic risk factors for depression has not been easy. Over a decade of genetic research did not yield a single replicable genetic factor for depression. It was only recently that 15 common genetic variants mostly in the non-coding parts of the genome were identified through a large genome-wide association study performed by 23andMe. All of these variants add a very small risk to depression individually (odds ratio < 1.05). These common variants cannot explain the cases that have a family history of depression.

Our hypothesis is that such familial cases are enriched for variants that are rare, lie in the coding region of the genome and thus have a large effect on depression. Such variants are enriched in families and isolated populations and therefore have a higher chance of being discovered compared to more cosmopolitan populations. Through gene-based analysis of rare coding variants we have identified a novel gene NKPD1 that may be relevant for depression. Further, we have noticed that the more deleterious the effect of the variant is on the protein, the larger the effect is on depressive symptoms.

MedicalResearch.com: What should readers take away from your report?

Response: I think the primary message is that depression is a disease where there may be multiple rare coding variants are involved, as opposed to the common disease common variant hypothesis. And that there is a large scope for personalized medicine.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: In genetic research on depression, I think researchers should now focus on identifying rare genetic variants in even larger samples. Investments in sequencing studies are needed.

MedicalResearch.com: Is there anything else you would like to add?

Response: This study is supported by the Netherlands Brain Foundation.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.


Najaf Amin, Nadezhda M. Belonogova, Olivera Jovanova, Rutger W.W. Brouwer, Jeroen G.J. van Rooij, Mirjam C.G.N. van den Hout, Gulnara R. Svishcheva, Robert Kraaij, Irina V. Zorkoltseva, Anatoly V. Kirichenko, Albert Hofman, André G. Uitterlinden, Wilfred F.J. van IJcken, Henning Tiemeier, Tatiana I. Axenovich, Cornelia M. van Duijn. Nonsynonymous Variation in NKPD1 Increases Depressive Symptoms in European Populations. Biological Psychiatry, 2017; 81 (8): 702 DOI: 10.1016/j.biopsych.2016.08.008

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Last Updated on April 6, 2017 by Marie Benz MD FAAD