Shared genetic influences on depression and menopause symptoms.
Shared genetic influences on depression and menopause symptoms.
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DOI：
10.1017/s0033291721004037
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发表时间：
2023-04
影响因子：
6.9
通讯作者：
Duncan, Laramie E.
中科院分区：
文献类型：
--
作者：
Meijsen, Joeri J.;Shen, Hanyang;Vemuri, Mytilee;Rasgon, Natalie L.;Koenen, Karestan C.;Duncan, Laramie E.
关键词：
女性经历严重抑郁和创伤后应激障碍(PTSD)的频率大约是男性的两倍。雌激素被认为是导致这些疾病的性别差异的原因，而雌激素减少也被认为是导致更年期症状(如潮热)的关键驱动因素。此外，雌激素还用于治疗更年期症状。为了测试更年期症状和精神障碍之间潜在的共同遗传影响，我们在英国生物库中进行了一项雌激素药物使用(作为更年期症状的替代品)的GWA。这项分析包括英国生物库中年龄在39岁至71岁之间的232,993名女性。基因分析的结果变量是雌激素药物的使用，不包括使用激素避孕药的女性。对欧洲血统GWAs结果进行了跨系GWAMeta分析和遗传相关分析。荷尔蒙的使用也被测试与抑郁和创伤后应激障碍的关系。使用雌激素药物的妇女(与不使用雌激素的妇女相比)发现了TACR3基因中的一个基因位点，该基因以前与更年期潮热有关(TOP rs77322567，OR=0.78，p=7.7x10−15)。遗传相关分析显示更年期症状和抑郁有共同的遗传影响(Rg=0.231，SE=0.055，p=2.8×10−5)。非遗传分析显示，在使用雌激素药物的女性中，精神症状得分较高。这些结果表明，更年期症状具有复杂的遗传病因，这与抑郁症的遗传影响部分相同。此外，这里发现的TACR3基因具有直接的临床相关性；神经激肽3受体的拮抗剂(由TACR3编码)是治疗潮热的有效药物。
Women experience major depression and post-traumatic stress disorder (PTSD) approximately twice as often as men. Estrogen is thought to contribute to sex differences in these disorders, and reduced estrogen is also known to be a key driver of menopause symptoms such as hot flashes. Moreover, estrogen is used to treat menopause symptoms. In order to test for potential shared genetic influences between menopause symptoms and psychiatric disorders, we conducted a GWAS of estrogen medication use (as a proxy for menopause symptoms) in the UK Biobank. The analysis included 232,993 women aged 39–71 in the UK Biobank. The outcome variable for genetic analyses was estrogen medication use, excluding women using hormonal contraceptives. Trans-ancestry GWAS meta-analyses were conducted along with genetic correlation analyses on the European ancestry GWAS results. Hormone usage was also tested for association with depression and PTSD. GWAS of estrogen medication use (compared to non-use) identified a locus in the TACR3 gene, which was previously linked to hot flashes in menopause (top rs77322567, OR=.78, p=7.7×10−15). Genetic correlation analyses revealed shared genetic influences on menopause symptoms and depression (rg=0.231, s.e.=0.055, p=2.8×10−5). Non-genetic analyses revealed higher psychiatric symptoms scores among women using estrogen medications. These results suggest that menopause symptoms have a complex genetic etiology which is partially shared with genetic influences on depression. Moreover, the TACR3 gene identified here has direct clinical relevance; antagonists for the neurokinin 3 receptor (coded for by TACR3) are effective treatments for hot flashes.