An Italian association study and meta-analysis with previous GWAS confirmWNT4,CDKN2BASandFN1as the first identified susceptibility loci for endometriosis

Abstract

We confirm WNT4, CDKN2BAS and FN1 as the first identified common loci for endometriosis.

A Rare Familial Case of Endometriosis with Very Severe Gynecological and Obstetric Complications: Novel Genetic Variants at a Glance

“…In addition, as reported in a recent study by Pagliardini et al [7], more severe stages of the disease were associated with a higher frequency of the risk allele G of rs1333049 in the CDKN2BAS locus.…”

“…Recently, based on the results of few genome-wide association studies (GWAS), few genetic susceptibility loci have been identified as associated robustly with the disease, thus opening a new era in the context of the discovery of genes predisposing to endometriosis [5,6]. Our replication analysis in an Italian population considering 4 of these polymorphisms allowed us to confirm 3 of these gene variants, rs7521902 close to WNT4 , rs1250248 within the fibronectin 1 ( FN1 ) gene and rs1333049 in the CDKN2BAS locus as common loci involved in the susceptibility to endometriosis [7]. However, despite the natural excitement emerging from these novel findings, mechanisms underlying genotype-phenotype relationships are totally unknown so far.…”

“…Specifically, based on the results of the 2 GWAS conducted for endometriosis in 2 different ethnic populations [5,6] and of a replication study on the Italian population [7], the following SNPs were considered:…”

Association of WNT4 polymorphisms with endometriosis in infertile patients

“…The relationship between rs2235529 and endometriosis was previously observed in North American and Chinese Han women [9,19]. Similarly, the rs7521902 was associated with endometriosis susceptibility in British, Australian, Italian, and Japanese women [21,22,8], but not in Belgian women [23]. The lack of an association between these two polymorphisms and endometriosis may be caused by the different genetic backgrounds of the Brazilian cohort that is considered as a highly admixed population [24].…”

Independent Replication and Meta-Analysis for Endometriosis Risk Loci

“…The three replication studies (Pagliardini et al, 2013(Pagliardini et al, , 2015Sundqvist et al, 2013) performed to date have only replicated association of rs7521902 (p = 5.6 × 10 −3 ; Pagliardini et al, 2013) and rs10859871 (p = 6.9 × 10 −5 ; Pagliardini et al, 2015) with endometriosis. Inherently hidden fine stratification among different populations of similar ancestry, which is often difficult to tease apart, power, and possible variations in disease definition and/or classification may have contributed to these inconsistent results.…”