Gardiner, SL;
van Belzen, MJ;
Boogaard, MW;
van Roon-Mom, WMC;
Rozing, MP;
van Hemert, AM;
Smit, JH;
... Aziz, NA; + view all
(2017)
Huntingtin gene repeat size variations affect risk of lifetime depression.
Translational Psychiatry
, 7
, Article 1277. 10.1038/s41398-017-0042-1.
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Abstract
Huntington disease (HD) is a severe neuropsychiatric disorder caused by a cytosine-adenine-guanine (CAG) repeat expansion in the HTT gene. Although HD is frequently complicated by depression, it is still unknown to what extent common HTT CAG repeat size variations in the normal range could affect depression risk in the general population. Using binary logistic regression, we assessed the association between HTT CAG repeat size and depression risk in two well-characterized Dutch cohorts─the Netherlands Study of Depression and Anxiety and the Netherlands Study of Depression in Older Persons─including 2165 depressed and 1058 non-depressed persons. In both cohorts, separately as well as combined, there was a significant non-linear association between the risk of lifetime depression and HTT CAG repeat size in which both relatively short and relatively large alleles were associated with an increased risk of depression (β = −0.292 and β = 0.006 for the linear and the quadratic term, respectively; both P < 0.01 after adjustment for the effects of sex, age, and education level). The odds of lifetime depression were lowest in persons with a HTT CAG repeat size of 21 (odds ratio: 0.71, 95% confidence interval: 0.52 to 0.98) compared to the average odds in the total cohort. In conclusion, lifetime depression risk was higher with both relatively short and relatively large HTT CAG repeat sizes in the normal range. Our study provides important proof-of-principle that repeat polymorphisms can act as hitherto unappreciated but complex genetic modifiers of depression.
| Type: | Article |
|---|---|
| Title: | Huntingtin gene repeat size variations affect risk of lifetime depression |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41398-017-0042-1 |
| Publisher version: | http://dx.doi.org/10.1038/s41398-017-0042-1 |
| Language: | English |
| Additional information: | Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Psychiatry, PITUITARY-ADRENAL AXIS, TRINUCLEOTIDE REPEAT, OLDER PERSONS, MOUSE MODEL, CAG LENGTH, DISEASE, SYMPTOMS, DISORDER, BEHAVIOR, POLYGLUTAMINE |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10041694 |
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