Institut Cochin, U1016 INSERM, UMR8104 CNRS and Université de Paris, 24 rue du Faubourg St-Jacques, 75014 Paris, France.
Int J Mol Sci. 2021 Jul 7;22(14):7297. doi: 10.3390/ijms22147297.
This review aims at better understanding the genetics of endometriosis. Endometriosis is a frequent feminine disease, affecting up to 10% of women, and characterized by pain and infertility. In the most accepted hypothesis, endometriosis is caused by the implantation of uterine tissue at ectopic abdominal places, originating from retrograde menses. Despite the obvious genetic complexity of the disease, analysis of sibs has allowed heritability estimation of endometriosis at ~50%. From 2010, large Genome Wide Association Studies (GWAS), aimed at identifying the genes and loci underlying this genetic determinism. Some of these loci were confirmed in other populations and replication studies, some new loci were also found through meta-analyses using pooled samples. For two loci on chromosomes 1 (near CCD42) and chromosome 9 (near CDKN2A), functional explanations of the SNP (Single Nucleotide Polymorphism) effects have been more thoroughly studied. While a handful of chromosome regions and genes have clearly been identified and statistically demonstrated as at-risk for the disease, only a small part of the heritability is explained (missing heritability). Some attempts of exome sequencing started to identify additional genes from families or populations, but are still scarce. The solution may reside inside a combined effort: increasing the size of the GWAS designs, better categorize the clinical forms of the disease before analyzing genome-wide polymorphisms, and generalizing exome sequencing ventures. We try here to provide a vision of what we have and what we should obtain to completely elucidate the genetics of this complex disease.
这篇综述旨在深入了解子宫内膜异位症的遗传学。子宫内膜异位症是一种常见的女性疾病，影响多达 10%的女性，其特征是疼痛和不孕。在最被接受的假说中，子宫内膜异位症是由子宫组织在异位的腹部位置植入引起的，源于逆行月经。尽管该疾病具有明显的遗传复杂性，但对同卵双胞胎的分析允许对子宫内膜异位症的遗传性进行约 50%的估计。自 2010 年以来，进行了大规模全基因组关联研究（GWAS），旨在确定导致这种遗传决定因素的基因和基因座。其中一些基因座在其他人群中得到了证实，在使用合并样本进行的荟萃分析中也发现了一些新的基因座。对于染色体 1（靠近 CCD42）和染色体 9（靠近 CDKN2A）上的两个基因座，对 SNP（单核苷酸多态性）效应的功能解释进行了更深入的研究。虽然一些染色体区域和基因已被明确确定并在统计学上证明与该疾病相关，但仅解释了一小部分遗传性（遗传缺失）。一些外显子测序的尝试已经开始从家族或人群中识别其他基因，但仍然很少。解决方案可能在于共同努力：增加 GWAS 设计的规模，在分析全基因组多态性之前更好地分类疾病的临床形式，并推广外显子测序的尝试。我们在这里尝试提供一个愿景，说明我们已经拥有的和我们应该获得的，以完全阐明这种复杂疾病的遗传学。
