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Transl Psychiatry. 2017 Dec 11;7(12):1277. doi: 10.1038/s41398-017-0042-1.

Huntingtin gene repeat size variations affect risk of lifetime depression.

Author information

1
Departments of Neurology, Leiden University Medical Centre, Leiden, The Netherlands.
2
Departments of Human Genetics, Leiden University Medical Centre, Leiden, The Netherlands.
3
Departments of Clinical Genetics, and Leiden University Medical Centre, Leiden, The Netherlands.
4
Department of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark.
5
Departments of Psychiatry, Leiden University Medical Centre, Leiden, The Netherlands.
6
Department of Psychiatry, and EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam, The Netherlands.
7
Department of Psychiatry, University Medical Centre Groningen, Groningen, The Netherlands.
8
Department of Psychiatry, Collaborative Antwerp Psychiatric Research Institute (CAPRI), University of Antwerp, Antwerp, Belgium.
9
Departments of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. N.A.Aziz@lumc.nl.
10
Department of Neurodegenerative Disease, UCL Huntington's Disease Centre, University College London Institute of Neurology, London, United Kingdom. N.A.Aziz@lumc.nl.

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.

PMID:
29225330
PMCID:
PMC5802693
DOI:
10.1038/s41398-017-0042-1
[Indexed for MEDLINE]
Free PMC Article

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