Sapkota Yadav, Attia John, Gordon Scott D, Henders Anjali K, Holliday Elizabeth G, Rahmioglu Nilufer, MacGregor Stuart, Martin Nicholas G, McEvoy Mark, Morris Andrew P, Scott Rodney J, Zondervan Krina T, Montgomery Grant W, Nyholt Dale R
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
Centre for Clinical Epidemiology and Biostatistics, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia Public Health Research Program, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
Mol Hum Reprod. 2015 Jul;21(7):594-602. doi: 10.1093/molehr/gav021. Epub 2015 Apr 16.
Endometriosis is primarily characterized by the presence of tissue resembling endometrium outside the uterine cavity and is usually diagnosed by laparoscopy. The most commonly used classification of disease, the revised American Fertility Society (rAFS) system to grade endometriosis into different stages based on disease severity (I to IV), has been questioned as it does not correlate well with underlying symptoms, posing issues in diagnosis and choice of treatment. Using two independent European genome-wide association (GWA) datasets and top-level classification of the endometriosis cases based on rAFS [minimal or mild (Stage A) and moderate-to-severe (Stage B) disease], we previously showed that Stage B endometriosis has greater contribution of common genetic variation to its aetiology than Stage A disease. Herein, we extend our previous analysis to four endometriosis stages [minimal (Stage I), mild (Stage II), moderate (Stage III) and severe (Stage IV) disease] based on the rAFS classification system and compared the genetic burden across stages. Our results indicate that genetic burden increases from minimal to severe endometriosis. For the minimal disease, genetic factors may contribute to a lesser extent than other disease categories. Mild and moderate endometriosis appeared genetically similar, making it difficult to tease them apart. Consistent with our previous reports, moderate and severe endometriosis showed greater genetic burden than minimal or mild disease. Overall, our results provide new insights into the genetic architecture of endometriosis and further investigation in larger samples may help to understand better the aetiology of varying degrees of endometriosis, enabling improved diagnostic and treatment modalities.
子宫内膜异位症的主要特征是子宫腔外存在类似子宫内膜的组织,通常通过腹腔镜检查进行诊断。最常用的疾病分类方法,即修订后的美国生育协会(rAFS)系统,根据疾病严重程度(I至IV期)对子宫内膜异位症进行分级,但由于其与潜在症状的相关性不佳,在诊断和治疗选择方面存在问题,因此受到质疑。我们此前利用两个独立的欧洲全基因组关联(GWA)数据集,并基于rAFS对子宫内膜异位症病例进行顶级分类[轻微或轻度(A期)和中度至重度(B期)疾病],发现B期子宫内膜异位症在病因学上比A期疾病受常见基因变异的影响更大。在此,我们基于rAFS分类系统将之前的分析扩展至四个子宫内膜异位症阶段[轻微(I期)、轻度(II期)、中度(III期)和重度(IV期)疾病],并比较了各阶段的遗传负担。我们的结果表明,遗传负担从轻微到重度子宫内膜异位症逐渐增加。对于轻微疾病,遗传因素的作用程度可能低于其他疾病类别。轻度和中度子宫内膜异位症在遗传上似乎相似,难以区分。与我们之前的报告一致,中度和重度子宫内膜异位症的遗传负担比轻微或轻度疾病更大。总体而言,我们的结果为子宫内膜异位症的遗传结构提供了新的见解,在更大样本中进行进一步研究可能有助于更好地理解不同程度子宫内膜异位症的病因,从而改进诊断和治疗方式。