Genetic burden associated with varying degrees of disease severity in endometriosis

被引:28
作者
Sapkota, Yadav [1 ]
Attia, John [2 ,3 ]
Gordon, Scott D. [1 ]
Henders, Anjali K. [1 ]
Holliday, Elizabeth G. [2 ,3 ]
Rahmioglu, Nilufer [4 ]
MacGregor, Stuart [1 ]
Martin, Nicholas G. [1 ]
McEvoy, Mark [2 ,3 ]
Morris, Andrew P. [4 ]
Scott, Rodney J. [3 ,5 ,6 ]
Zondervan, Krina T. [4 ,7 ]
Montgomery, Grant W. [1 ]
Nyholt, Dale R. [1 ,8 ]
机构
[1] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia
[2] Univ Newcastle, Ctr Clin Epidemiol & Biostat, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia
[3] Hunter Med Res Inst, Publ Hlth Res Program, Newcastle, NSW, Australia
[4] Univ Oxford, Wellcome Trust Ctr Human Genet, Genet & Genom Epidemiol Unit, Oxford, England
[5] Univ Newcastle, Sch Biomed Sci & Pharm, Newcastle, NSW 2300, Australia
[6] Hunter Area Pathol Serv, Div Genet, Newcastle, NSW, Australia
[7] Univ Oxford, John Radcliffe Hosp, Nuffield Dept Obstet & Gynaecol, Oxford OX3 9DU, England
[8] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia
基金
英国医学研究理事会; 英国惠康基金; 澳大利亚国家健康与医学研究理事会;
关键词
endometriosis; rAFS classification system; genetic burden; polygenic prediction; genome-wide association studies; GENOME-WIDE ASSOCIATION; DIAGNOSIS; STAGE; TWIN;
D O I
10.1093/molehr/gav021
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:594 / 602
页数:9
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