Division of Endocrinology, Boston Children's Hospital, Boston, MA 02115, USA.
Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1577-e1587. doi: 10.1210/clinem/dgab838.
Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism and can be associated with cardiometabolic dysfunction, but it remains unclear which of these features are inciting causes and which are secondary consequences.
To determine whether ovarian function is necessary for genetic risk factors for PCOS to produce nonreproductive phenotypes.
DESIGN, SETTING, AND PARTICIPANTS: Cohort of 176 360 men in the UK Biobank and replication cohort of 37 348 men in the Estonian Biobank.
We calculated individual PCOS polygenic risk scores (PRS), tested for association of these PRS with PCOS-related phenotypes using linear and logistic regression and performed mediation analysis.
For every 1 SD increase in the PCOS PRS, men had increased odds of obesity (odds ratio [OR]: 1.09; 95% CI, 1.08-1.10; P = 1 × 10-49), type 2 diabetes mellitus (T2DM) (OR: 1.08; 95% CI, 1.05-1.10; P = 3 × 10-12), coronary artery disease (CAD) (OR: 1.03; 95% CI, 1.01-1.04; P = 0.0029), and marked androgenic alopecia (OR: 1.03; 95% CI, 1.02-1.05; P = 3 × 10-5). Body mass index (BMI), hemoglobin A1c, triglycerides, and free androgen index increased as the PRS increased, whereas high-density lipoprotein cholesterol and SHBG decreased (all P < .0001). The association between the PRS and CAD appeared to be completely mediated by BMI, whereas the associations with T2DM and marked androgenic alopecia appeared to be partially mediated by BMI.
Genetic risk factors for PCOS have phenotypic consequences in men, indicating that they can act independently of ovarian function. Thus, PCOS in women may not always be a primary disorder of the ovaries.
多囊卵巢综合征（PCOS）的特征是排卵功能障碍和高雄激素血症，并且可能与心脏代谢功能障碍相关，但目前尚不清楚这些特征中哪些是激发因素，哪些是继发后果。
确定卵巢功能是否是 PCOS 遗传风险因素产生非生殖表型的必要条件。
设计、地点和参与者：英国生物库中的 176360 名男性队列和爱沙尼亚生物库中的 37348 名男性复制队列。
我们计算了个体 PCOS 多基因风险评分（PRS），使用线性和逻辑回归检验这些 PRS 与 PCOS 相关表型的关联，并进行了中介分析。
PRS 每增加 1 个标准差，男性肥胖的几率就会增加（比值比 [OR]：1.09；95%置信区间 [CI]：1.08-1.10；P = 1×10-49）、2 型糖尿病（T2DM）（OR：1.08；95%CI：1.05-1.10；P = 3×10-12）、冠心病（CAD）（OR：1.03；95%CI：1.01-1.04；P = 0.0029）和明显的雄激素性脱发（OR：1.03；95%CI：1.02-1.05；P = 3×10-5）。随着 PRS 的增加，体重指数（BMI）、糖化血红蛋白、甘油三酯和游离雄激素指数增加，而高密度脂蛋白胆固醇和 SHBG 降低（均 P <.0001）。PRS 与 CAD 之间的关联似乎完全由 BMI 介导，而与 T2DM 和明显的雄激素性脱发之间的关联似乎部分由 BMI 介导。
PCOS 的遗传风险因素在男性中具有表型后果，表明它们可以独立于卵巢功能发挥作用。因此，女性的 PCOS 可能并不总是卵巢的原发性疾病。
