Genome-wide meta-analysis of heavy menstrual bleeding reveals 36 risk loci.

To better characterize the genetic architecture of HMB, we conducted a meta-analysisof the summary statistics of genome-wide association studies (GWAS) from 5 biobanks that included up to 84 633 HMB cases and 598 195 controls from several ancestries.

为了更好地描述月经过多（HMB）的遗传结构，我们对来自5个生物库的全基因组关联研究（GWAS）的汇总统计数据进行了荟萃分析，这些生物库包括最多84,633例HMB病例和598,195例对照，涉及多个种族背景。

Of the 21 signals significantly associated with HMB in a discovery GWAS meta-analysisthat combined 4 biobanks, 20 had a concordant direction of effect in the remaining cohort, including 10 that were significantly replicated.

在将4个生物样本库合并的发现性全基因组关联研究(GWAS)荟萃分析中，与HMB显著相关的21个信号中，有20个在剩余队列中效应方向一致，包括10个显著复制的信号。

By combining the discovery and replication data sets, 15 additional signals were identified in subsequent meta-analyses.

通过结合发现和复制数据集，在随后的荟萃分析中鉴定了15个额外的信号。

These genetic analyses identified 36 signals (33 novel) that were significantly associated with HMB, and gene prioritization techniques (eg, transcriptome-wide association studies, polygenic priority score) subsequently revealed likely causal genes.

这些遗传分析确定了与HMB显著相关的36个信号（其中33个是新的），随后的基因优先排序技术（例如，全转录组关联研究，多基因优先分数）揭示了可能的因果基因。

Notable discoveries included the strong protective effect of the F5-Leiden variant (rs6025-T; odds ratio, 0.75; P = 6.8 × 10-33); variants at the FSHB and LHB/CGB loci, both involved in hormone production regulation; and several signals near genes involved in the Wnt/β-catenin signaling pathway.

重要的发现包括F5-Leiden变异（rs6025-T；比值比，0.75；P = 6.8 × 10^-33）的强烈保护作用；FSHB和LHB/CGB位点的变异，这两个位点都涉及激素产生的调节；以及几个位于Wnt/β-catenin信号通路相关基因附近的信号。

We also observed strong and significant genetic correlations with disorders of the female genital tract, including uterine fibroids, endometriosis, or ovarian cysts.

我们还观察到与女性生殖道疾病，包括子宫肌瘤、子宫内膜异位症或卵巢囊肿，有强烈且显著的遗传相关性。

Overall, we identified 33 novel genetic loci associated with HMB, thereby significantly improving our understanding of the genetic etiology of this condition, which may provide new targets for the development of therapeutic strategies.

总体而言，我们确定了与月经过多相关的33个新的遗传位点，从而显著提高了我们对这种状况遗传病因的理解，这可能为开发治疗策略提供新的靶点。