Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI.
Department of Medicine, David Geffen School of Medicine at University of California, Los Angeles, CA.
Menopause. 2021 Apr 26;28(8):883-892. doi: 10.1097/GME.0000000000001785.
Vasomotor symptoms (VMS), hot flashes, and night sweats are cardinal symptoms of the menopausal transition. Little is known about genetic influences on VMS. This study evaluated whether previously identified genetic factors predictive of VMS, age at menarche, and age at menopause were associated with VMS in a multiracial/ethnic cohort.
For 702 White, 306 Black, 126 Chinese, and 129 Japanese women from the Study of Women's Health Across the Nation (SWAN) Genomic Substudy, we created polygenic risk scores (PRSs) from genome-wide association studies of VMS and ages at menarche and menopause. PRSs and single nucleotide polymorphisms (SNPs) from a previously identified VMS locus (tachykinin receptor 3 [TACR3]) were evaluated for associations with frequent VMS (VMS ≥6 days in the past 2 weeks at any visit) and with VMS trajectories (persistently low, early onset, final menstrual period onset, persistently high).
The C-allele of rs74827081 in TACR3 was associated with reduced likelihood of frequent VMS in White women (odds ratio [OR] = 0.49 [95% CI, 0.29-0.83]). With higher menarche PRS (later menarche), Black women were less likely (OR = 0.55 [95% CI, 0.38-0.78]) to report frequent VMS. With higher PRS for age at menarche, Black women were also less likely to have a persistently high VMS trajectory (OR = 0.55 [95% CI, 0.34-0.91]), whereas White women (OR = 0.75 [95% CI, 0.58-0.98]) were less likely to have a final menstrual period onset trajectory (vs persistently low). Chinese women with higher menopause PRS were more likely to have frequent VMS (OR = 2.29 [95% CI, 1.39-3.78]). Associations were substantively similar after excluding rs74827081 C-allele carriers.
Genetic factors predictive of reproductive aging are also associated with VMS, suggesting that VMS have a polygenic architecture. Further study in this area may help to identify new targets for novel VMS therapies.
血管舒缩症状（VMS）、热潮和盗汗是绝经过渡期的主要症状。遗传对 VMS 的影响知之甚少。本研究评估了先前确定的与 VMS、初潮年龄和绝经年龄相关的遗传因素是否与多种族/族裔队列中的 VMS 相关。
在来自女性健康研究 across the Nation（SWAN）基因组子研究的 702 名白人、306 名黑人、126 名中国人和 129 名日本人妇女中，我们从 VMS 和初潮和绝经年龄的全基因组关联研究中创建了多基因风险评分（PRSs）。评估了先前确定的 VMS 基因座（速激肽受体 3[TACR3]）中的PRS 和单核苷酸多态性（SNP）与频繁 VMS（在任何访视中过去 2 周内 VMS 天数≥6 天）和 VMS 轨迹（持续低、早发、绝经起始、持续高）的相关性。
TACR3 中的 rs74827081 的 C 等位基因与白人妇女中频繁 VMS 的可能性降低相关（优势比[OR]＝0.49[95%置信区间，0.29-0.83]）。随着初潮 PRS（较晚初潮）的增加，黑人妇女报告频繁 VMS 的可能性较低（OR＝0.55[95%置信区间，0.38-0.78]）。随着初潮年龄 PRS 的增加，黑人妇女也不太可能出现持续高 VMS 轨迹（OR＝0.55[95%置信区间，0.34-0.91]），而白人妇女（OR＝0.75[95%置信区间，0.58-0.98]）不太可能出现绝经起始轨迹（与持续低相比）。绝经 PRS 较高的中国妇女更有可能出现频繁的 VMS（OR＝2.29[95%置信区间，1.39-3.78]）。排除 rs74827081 的 C 等位基因携带者后，关联基本相似。
预测生殖衰老的遗传因素也与 VMS 相关，这表明 VMS 具有多基因结构。该领域的进一步研究可能有助于为新的 VMS 治疗方法确定新的靶点。
