TY - JOUR
T1 - Causal relationship between polycystic ovary syndrome and coronary artery disease
T2 - A Mendelian randomisation study
AU - Simons, Pomme I H G
AU - Cornelissen, Merel E.B.
AU - Valkenburg, Olivier
AU - Onland-Moret, N Charlotte
AU - van der Schouw, Yvonne T
AU - Stehouwer, Coen D A
AU - Burgess, Stephen
AU - Brouwers, Martijn C G J
N1 - Funding Information:
This study was supported by a research grant from the European Foundation for the Study of Diabetes/Sanofi.
Publisher Copyright:
© 2021 The Authors. Clinical Endocrinology Published by John Wiley & Sons Ltd
PY - 2022/4
Y1 - 2022/4
N2 - OBJECTIVE: Polycystic ovary syndrome (PCOS) has been associated with an increased risk of coronary artery disease (CAD). However, it remains uncertain whether this increased risk is the result of PCOS per se or, alternatively, is explained by obesity, a common feature of PCOS. The aim of this study was to assess the causal association between PCOS and CAD and the role of obesity herein.DESIGN AND METHODS: We conducted two-sample Mendelian randomisation analyses in large-scale, female-specific datasets to study the association between genetically predicted (1) risk of PCOS and risk of CAD, (2) body mass index (BMI) and risk of PCOS and (3) BMI and risk of CAD. Primary analyses were conducted with the inverse-variance weighted (IVW) method. Simple median, penalized weighted median and contamination mixture analyses were performed to assess the robustness of the outcomes.RESULTS: IVW analyses did not show a statistically significant association between PCOS and CAD (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.89, 1.11). In contrast, genetically predicted BMI was statistically significantly associated with an increased odds of PCOS (OR: 3.21, 95% CI: 2.26, 4.56) and CAD (OR: 1.38, 95% CI: 1.14, 1.67). Similar results were obtained when secondary analyses were performed.CONCLUSION: These sex-specific analyses show that the genetically predicted risk of PCOS is not associated with the risk of CAD. Instead, the genetically predicted risk of obesity (and its downstream metabolic effects) is the common denominator of both PCOS and CAD risk.
AB - OBJECTIVE: Polycystic ovary syndrome (PCOS) has been associated with an increased risk of coronary artery disease (CAD). However, it remains uncertain whether this increased risk is the result of PCOS per se or, alternatively, is explained by obesity, a common feature of PCOS. The aim of this study was to assess the causal association between PCOS and CAD and the role of obesity herein.DESIGN AND METHODS: We conducted two-sample Mendelian randomisation analyses in large-scale, female-specific datasets to study the association between genetically predicted (1) risk of PCOS and risk of CAD, (2) body mass index (BMI) and risk of PCOS and (3) BMI and risk of CAD. Primary analyses were conducted with the inverse-variance weighted (IVW) method. Simple median, penalized weighted median and contamination mixture analyses were performed to assess the robustness of the outcomes.RESULTS: IVW analyses did not show a statistically significant association between PCOS and CAD (odds ratio [OR]: 0.99, 95% confidence interval [CI]: 0.89, 1.11). In contrast, genetically predicted BMI was statistically significantly associated with an increased odds of PCOS (OR: 3.21, 95% CI: 2.26, 4.56) and CAD (OR: 1.38, 95% CI: 1.14, 1.67). Similar results were obtained when secondary analyses were performed.CONCLUSION: These sex-specific analyses show that the genetically predicted risk of PCOS is not associated with the risk of CAD. Instead, the genetically predicted risk of obesity (and its downstream metabolic effects) is the common denominator of both PCOS and CAD risk.
KW - coronary artery disease
KW - Mendelian randomisation
KW - obesity
KW - polycystic ovary syndrome
UR - http://www.scopus.com/inward/record.url?scp=85115104960&partnerID=8YFLogxK
U2 - 10.1111/cen.14593
DO - 10.1111/cen.14593
M3 - Article
C2 - 34524719
SN - 0300-0664
VL - 96
SP - 599
EP - 604
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 4
ER -