Huntingtin gene repeat size variations affect risk of lifetime depression.
Huntingtin gene repeat size variations affect risk of lifetime depression.
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DOI：
10.1038/s41398-017-0042-1
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发表时间：
2017-12-11
影响因子：
6.8
通讯作者：
Aziz NA
中科院分区：
文献类型：
--
作者：
Gardiner SL;van Belzen MJ;Boogaard MW;van Roon-Mom WMC;Rozing MP;van Hemert AM;Smit JH;Beekman ATF;van Grootheest G;Schoevers RA;Oude Voshaar RC;Roos RAC;Comijs HC;Penninx BWJH;van der Mast RC;Aziz NA
亨廷顿病（HD）是由HTT基因中的胞嘧啶-腺嘌呤-鸟嘌呤（CAG）重复扩增引起的严重神经精神障碍。虽然HD经常并发抑郁症，但在正常范围内常见的HTT CAG重复序列大小变异在多大程度上会影响一般人群的抑郁症风险仍然是未知的。使用二元逻辑回归，我们评估了HTT CAG重复序列大小与两个特征良好的荷兰队列（荷兰抑郁和焦虑研究和荷兰老年人抑郁研究）中抑郁风险之间的关联，其中包括2165名抑郁症患者和1058名非抑郁症患者。在这两个队列中，无论是单独还是合并，终生抑郁的风险与HTT CAG重复序列大小之间存在显著的非线性相关性，其中相对较短和相对较大的等位基因均与抑郁风险增加相关（线性项和二次项分别为β =-0.292和0.006;调整性别、年龄和教育水平后，P均< 0.01）。与总队列的平均比值相比，HTT CAG重复大小为21的人终身抑郁的比值最低（比值比：0.71，95%置信区间：0.52至0.98）。总之，在正常范围内，HTT CAG重复长度相对较短和相对较大的患者终生抑郁风险较高。我们的研究提供了重要的原则证明，重复多态性可以作为迄今未被认识到的，但复杂的抑郁症遗传修饰剂。
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.
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影响因子：
3.1
作者：
Andrade, L;Caraveo-Anduaga, JJ;Wittchen, HU
通讯作者：
Wittchen, HU
影响因子：
25
作者：
Langfelder P;Cantle JP;Chatzopoulou D;Wang N;Gao F;Al-Ramahi I;Lu XH;Ramos EM;El-Zein K;Zhao Y;Deverasetty S;Tebbe A;Schaab C;Lavery DJ;Howland D;Kwak S;Botas J;Aaronson JS;Rosinski J;Coppola G;Horvath S;Yang XW
通讯作者：
Yang XW
影响因子：
5.8
作者：
Aziz, N. Ahmad;Pijl, Hanno;Roos, Raymund A. C.
通讯作者：
Roos, Raymund A. C.
影响因子：
3.5
作者：
Langbehn, DR;Brinkman, RR;Hayden, MR
通讯作者：
Hayden, MR
影响因子：
6.8
作者：
Gardiner, S. L.;van Belzen, M. J.;Aziz, N. A.
通讯作者：
Aziz, N. A.