■子宫内膜异位症是妇女在其生育期的慢性炎症性疾病。子宫内膜异位症的严重程度和部位与月经的关系,排卵,生殖功能,和交付方式仍不清楚。
■我们探索了子宫内膜异位症的各种表型与月经之间的关联,排卵,生殖功能,和交付方式,使用两个样本孟德尔随机化(MR)和来自FinnGen联盟和女性月经的子宫内膜异位症分期和位置的汇总数据,排卵,生殖功能,以及OpenGWAS和ReproGen的交付模式。将逆方差加权用于主要MR分析。此外,一系列的敏感性分析,混杂分析,共同定位分析,并进行了多变量MR分析。
■MR分析显示,中度至重度子宫内膜异位症对最后一次活产年龄(OR=0.973,95%CI:0.960-0.986)和正常分娩(OR=0.999,95%CI:0.998-1.000;终点值被排除在外),卵巢子宫内膜异位症的最后一次活产年龄(OR=0.976,95%CI:0.965-0.988)和正常分娩(OR=0.999,95%CI:0.998-1.000;排除终点值),输卵管子宫内膜异位症与月经不调有关(OR=0.966,95%CI:0.942-0.990)。双向MR分析显示,初潮年龄对肠道子宫内膜异位症有负面影响(OR=0.417,95%CI:0.216-0.804)。所有MR分析均通过敏感性分析确认,只有中度至重度子宫内膜异位症对正常分娩和最后一次活产年龄的遗传影响得到了共同定位证据的支持。
■我们的发现加深了对各种类型的子宫内膜异位症与月经之间关系的理解,排卵,生殖功能,明确中重度子宫内膜异位症的重要作用。
UNASSIGNED: Endometriosis is a chronic inflammatory disease of women during their reproductive years. The relationship between the severity and location of endometriosis and menstruation,
ovulation, reproductive function, and mode of delivery remains unclear.
UNASSIGNED: We explored the association between the various phenotypes of endometriosis and menstruation,
ovulation, reproductive function, and mode of delivery, using two-sample Mendelian randomization (MR) and summary data on endometriosis stages and locations from the FinnGen consortium and women\'s menstruation,
ovulation, reproductive function, and mode of delivery from OpenGWAS and ReproGen. Inverse-variance weighting was used for the primary MR analysis. In addition, a series of sensitivity analyses, confounding analyses, co-localization analyses, and multivariate MR analyses were performed.
UNASSIGNED: MR analysis showed a negative effect of moderate to severe endometriosis on age at last live birth (OR = 0.973, 95% CI: 0.960-0.986) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), ovarian endometriosis on age at last live birth (OR = 0.976, 95% CI: 0.965-0.988) and normal delivery (OR = 0.999, 95% CI: 0.998-1.000; values for endpoint were excluded), and fallopian tubal endometriosis on excessive irregular menstruation (OR = 0.966, 95% CI: 0.942-0.990). Bidirectional MR analysis showed that age at menarche had a negative causal effect on intestinal endometriosis (OR = 0.417, 95% CI: 0.216-0.804). All MR analyses were confirmed by sensitivity analyses, and only the genetic effects of moderate to severe endometriosis on normal delivery and age at last live birth were supported by co-localization evidence.
UNASSIGNED: Our findings deepen the understanding of the relationship between various types of endometriosis and menstruation,
ovulation, reproductive function, and mode of delivery and clarify the important role of moderate to severe endometriosis.