Heritability of endometriosis

Saha, Rajesh; Pettersson, Hans; Svedberg, Pia; Olovsson, Matts; Bergqvist, Agneta; Marions, Lena; Tornvall, Per; Kuja‐Halkola, Ralf

doi:10.1016/j.fertnstert.2015.06.035

Cited by 137 publications

(112 citation statements)

References 42 publications

(47 reference statements)

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Among all confirmed cases, 80% were diagnosed surgically and 20% clinically. 2 We confirmed clinically diagnosed cases based on symptoms (severe dysmenorrhea, pelvic pain, dyspareunia, and infertility), physical examination, and sonography, since Ferrero et al 30 have shown that clinically suspected endometriosis (based on symptoms, physical examination, and sonography) could be confirmed by magnetic resonance imaging and/or surgery in 90% of the cases. Thus, self-reported endometriosis had acceptable validity, and we proceeded to perform analyses using the selfreported data.…”

Section: Study Population and Data Collectionsupporting

confidence: 69%

“…It is a complex trait with significant environmental and genetic influences that are likely to affect disease expression. 2,3 A number of menstrual and reproductive factors are suggested as risk factors or markers for endometriosis, such as earlier age at menarche, shorter menstrual cycle length, heavier menstrual volume, and nulliparity. [4][5][6][7][8][9][10][11] A link between use of oral contraceptives (OCs) and endometriosis is still uncertain.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample

Saha

Kuja‐Halkola

Tornvall

et al. 2017

Journal of Women's Health

Self Cite

View full text Add to dashboard Cite

Objectives: Despite the high prevalence of endometriosis among women of reproductive age, risk factors or markers for developing the condition remain largely unknown. Many of the published studies are based on small selected samples. We therefore investigated the relationships of reproductive and lifestyle factors with endometriosis in a large sample of Swedish female twins. Material and methods: This cross-sectional study included 28,822 women. Among these, endometriosis was reported by 1,228 women and the self-reported diagnosis was confirmed by medical records. Potential risk factors or markers for risk considered were age at menarche, level of education, body mass index (BMI), parity, oral contraceptive (OC) use, infertility, coffee consumption, smoking, and alcohol intake, which were investigated using logistic regression with crude and adjusted analyses. We performed within-pair analysis to examine the sensitivity of the results. Results: Late age at menarche and higher parity showed an inverse association and infertility showed a strong association with endometriosis. We observed positive associations with coffee consumption and smoking and an inverse association with OC use in crude analysis but not in adjusted analysis. There were no significant associations between level of education, BMI, or alcohol intake and endometriosis. Within-pair analysis showed persistent inverse association of parity and association of infertility with endometriosis. Conclusions: Our study suggests that late age at menarche and higher parity are inversely associated and infertility is strongly associated with endometriosis. Future studies are needed to explore the significance of these factors in the diagnosis of endometriosis and understanding of its etiology.

show abstract

Section: Study Population and Data Collectionsupporting

confidence: 69%

mentioning

confidence: 99%

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample

Saha

Kuja‐Halkola

Tornvall

et al. 2017

Journal of Women's Health

Self Cite

View full text Add to dashboard Cite

show abstract

“…The involvement of genetic factors in the development of endometriosis is supported by numerous studies (Simpson, et al ., 1980; Bischoff and Simpson, 2004; Rahmioglu et al ., 2015a, 2015b), and its heritability is estimated at ~50% (Treloar et al ., 1999; Saha et al ., 2015). Before the advent of GWAS, candidate gene association studies were the most common type of study in the investigation of genetic factors underlying complex diseases, and many such studies have been published for endometriosis (Rahmioglu, et al ., 2012; Montgomery et al ., 2014).…”

Section: Introductionmentioning

confidence: 99%

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

et al. 2017

View full text Add to dashboard Cite

STUDY QUESTIONDo genome-wide association study (GWAS) data for endometriosis provide insight into novel biological pathways associated with its pathogenesis?SUMMARY ANSWERGWAS analysis uncovered multiple pathways that are statistically enriched for genetic association signals, analysis of Stage A disease highlighted a novel variant in MAP3K4, while top pathways significantly associated with all endometriosis and Stage A disease included several mitogen-activated protein kinase (MAPK)-related pathways.WHAT IS KNOWN ALREADYEndometriosis is a complex disease with an estimated heritability of 50%. To date, GWAS revealed 10 genomic regions associated with endometriosis, explaining <4% of heritability, while half of the heritability is estimated to be due to common risk variants. Pathway analyses combine the evidence of single variants into gene-based measures, leveraging the aggregate effect of variants in genes and uncovering biological pathways involved in disease pathogenesis.STUDY DESIGN, SIZE, DURATIONPathway analysis was conducted utilizing the International Endogene Consortium GWAS data, comprising 3194 surgically confirmed endometriosis cases and 7060 controls of European ancestry with genotype data imputed up to 1000 Genomes Phase three reference panel. GWAS was performed for all endometriosis cases and for Stage A (revised American Fertility Society (rAFS) I/II, n = 1686) and B (rAFS III/IV, n = 1364) cases separately. The identified significant pathways were compared with pathways previously investigated in the literature through candidate association studies.PARTICIPANTS/MATERIALS, SETTING, METHODSThe most comprehensive biological pathway databases, MSigDB (including BioCarta, KEGG, PID, SA, SIG, ST and GO) and PANTHER were utilized to test for enrichment of genetic variants associated with endometriosis. Statistical enrichment analysis was performed using the MAGENTA (Meta-Analysis Gene-set Enrichment of variaNT Associations) software.MAIN RESULTS AND THE ROLE OF CHANCEThe first genome-wide association analysis for Stage A endometriosis revealed a novel locus, rs144240142 (P = 6.45 × 10−8, OR = 1.71, 95% CI = 1.23–2.37), an intronic single-nucleotide polymorphism (SNP) within MAP3K4. This SNP was not associated with Stage B disease (P = 0.086). MAP3K4 was also shown to be differentially expressed in eutopic endometrium between Stage A endometriosis cases and controls (P = 3.8 × 10−4), but not with Stage B disease (P = 0.26). A total of 14 pathways enriched with genetic endometriosis associations were identified (false discovery rate (FDR)-P < 0.05). The pathways associated with any endometriosis were Grb2-Sos provides linkage to MAPK signaling for integrins pathway (P = 2.8 × 10−5, FDR-P = 3.0 × 10−3), Wnt signaling (P = 0.026, FDR-P = 0.026) and p130Cas linkage to MAPK signaling for integrins pathway (P = 6.0 × 10−4, FDR-P = 0.029); with Stage A endometriosis: extracellular signal-regulated kinase (ERK)1 ERK2 MAPK (P = 5.0 × 10−4, FDR-P = 5.0 × 10−4) and with Stage B endometriosis: two overlappin...

show abstract

“…Генетическая предрасположенность к раз-витию эндометриоза описана многими авто-рами [10], феномен «семейного эндометри-оза» известен практикующим гинекологам. Это указывает на существование наследуемых генетических факторов, участвующих в разви-тии заболевания.…”

Section: наследуемые генетические признаки предрасположенности к эндоunclassified

Molecular-genetic background of endometriosis: diagnostic potential of heritable and expressed factors

et al. 2018

View full text Add to dashboard Cite

Endometriosis (EM) is a common disease in women of reproductive and perimenopausal age, characterized by the formation of ectopic foci of endometrial proliferation. The pathogenesis of the disease is multifactorial and has not been fully studied. Non-invasive examination methods have relative diagnostic value; therefore, current therapeutic approaches frequently do not provide a complete recovery. This situation determines the interest in studying the molecular and genetic background of EM and in searching for new diagnostic and prognostic markers. In this review, we briefly discuss the prevailing theories of EM etiology, taking into consideration modern scientific concepts. A separate chapter highlights the data of the genome-wide associative studies (GWAS) that indicate the possibilities of involving a number of genes in the pathogenesis of EM (WNT4, CDKN2BAS, FN1). The main part of the review is focused on the analysis of the gene expression studies comparing the ectopic and eutopic endometrium of women with EM. Considering the clinical significance, the results of three studies comparing expression profile of the eutopic endometrium of healthy women versus patients with EM are presented in detail. In conclusion, the prospects of the development and clinical application of heritable and expressed EM markers are assessed.

show abstract

Heritability of endometriosis

Abstract: Our findings suggest both genetic and unique (nonshared) environmental influences on the complex etiology of endometriosis and support the hypothesis that genes have a strong influence on phenotypic manifestations of endometriosis.

Cited by 137 publications

References 42 publications

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample

Reproductive and Lifestyle Factors Associated with Endometriosis in a Large Cross-Sectional Population Sample

Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis

Molecular-genetic background of endometriosis: diagnostic potential of heritable and expressed factors

Contact Info

Product

Resources

About