The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions
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DOI：
10.1038/s41588-023-01323-z
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发表时间：
2023-03-01
期刊：
影响因子：
30.8
通讯作者：
Zondervan, Krina T.
中科院分区：
文献类型：
--
作者：
Rahmioglu, Nilufer;Mortlock, Sally;Zondervan, Krina T.
子宫内膜异位症是一种常见的疾病与衰弱盆腔疼痛和不孕症。一项全基因组关联研究荟萃分析，包括欧洲和东亚血统的60，674例病例和701，926例对照，确定了42个全基因组显著位点，包括49个不同的关联信号。由卵巢子宫内膜异位症驱动的3/4期疾病的效应量最大。识别的信号解释了高达5.01%的疾病变异和子宫内膜和血液中基因的调节表达或甲基化，其中许多与疼痛感知/维持相关（SRP 14/BMF，GDAP 1，MLLT 10，BSN和NGF）。我们观察到子宫内膜异位症与11种疼痛疾病之间存在显著的遗传相关性，包括偏头痛，背部和多部位慢性疼痛（MCP），以及炎症性疾病，包括哮喘和骨关节炎。多性状遗传分析确定了与子宫内膜异位症和MCP/偏头痛相关的变异的实质性共享。有针对性的调查子宫内膜异位症和其他疼痛条件之间共享的遗传调控机制，以帮助开发新的治疗方法，并促进早期症状intervention. Meta分析子宫内膜异位症的全基因组关联研究确定49个不同的关联信号。因果变异的精细映射探索了各种组织的功能效应。子宫内膜异位症和其他疼痛状况之间的遗传相关性也被强调。
Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.Meta-analyses of genome-wide association studies for endometriosis identify 49 distinct association signals. Fine-mapping of causal variants explores functional effects across various tissues. Genetic correlations between endometriosis and other pain conditions are also highlighted.