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Open Access 01-12-2022 | Obesity | Research article

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Authors: Qianwen Liu, Zhaozhong Zhu, Peter Kraft, Qiaolin Deng, Elisabet Stener-Victorin, Xia Jiang

Published in: BMC Medicine | Issue 1/2022

Abstract

Background

The comorbidity between polycystic ovary syndrome (PCOS) and obesity has long been observed in clinical settings, but their shared genetic basis remains unclear.

Methods

Leveraging summary statistics of large-scale GWAS(s) conducted in European-ancestry populations on body mass index (adult BMI, N_female=434,794; childhood BMI, N=39,620), waist-to-hip ratio (WHR, N_female=381,152), WHR adjusted for BMI (WHR_adjBMI, N_female=379,501), and PCOS (N_case=10,074, N_control=103,164), we performed a large-scale genome-wide cross-trait analysis to quantify overall and local genetic correlation, to identify shared loci, and to infer causal relationship.

Results

We found positive genetic correlations between PCOS and adult BMI (r_g=0.47, P=2.19×10⁻¹⁶), childhood BMI (r_g=0.31, P=6.72×10⁻⁵), and WHR (r_g=0.32, P=1.34×10⁻¹⁰), all withstanding Bonferroni correction. A suggestive significant genetic correlation was found between PCOS and WHR_adjBMI (r_g=0.09, P=0.04). Partitioning the whole genome into 1703 nearly independent regions, we observed a significant local genetic correlation for adult BMI and PCOS at chromosome 18: 57630483–59020751. We identified 16 shared loci underlying PCOS and obesity-related traits via cross-trait meta-analysis including 9 loci shared between BMI and PCOS (adult BMI and PCOS: 5 loci; childhood BMI and PCOS: 4 loci), 6 loci shared between WHR and PCOS, and 5 loci shared between WHR_adjBMI and PCOS. Mendelian randomization (MR) supported the causal roles of both adult BMI (OR=2.92, 95% CI=2.33–3.67) and childhood BMI (OR=2.76, 95% CI=2.09–3.66) in PCOS, but not WHR (OR=1.19, 95% CI=0.93–1.52) or WHR_adjBMI (OR=1.03, 95% CI=0.87–1.22). Genetic predisposition to PCOS did not seem to influence the risk of obesity-related traits.

Conclusions

Our cross-trait analysis suggests a shared genetic basis underlying obesity and PCOS and provides novel insights into the biological mechanisms underlying these complex traits. Our work informs public health intervention by confirming the important role of weight management in PCOS prevention.

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Title: Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis
Authors: Qianwen Liu
Zhaozhong Zhu
Peter Kraft
Qiaolin Deng
Elisabet Stener-Victorin
Xia Jiang
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Obesity
Obesity
Polycystic Ovary Syndrome
Polycystic Ovary Syndrome
Published in: BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI: https://doi.org/10.1186/s12916-022-02238-y

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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