Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis
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 i...
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BMC
2022-02-01
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| Series: | BMC Medicine |
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| Online Access: | https://doi.org/10.1186/s12916-022-02238-y |
| _version_ | 1818330340829167616 |
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| author | Qianwen Liu Zhaozhong Zhu Peter Kraft Qiaolin Deng Elisabet Stener-Victorin Xia Jiang |
| author_facet | Qianwen Liu Zhaozhong Zhu Peter Kraft Qiaolin Deng Elisabet Stener-Victorin Xia Jiang |
| author_sort | Qianwen Liu |
| collection | DOAJ |
| description | 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 (WHRadjBMI, 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 WHRadjBMI (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 WHRadjBMI 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 WHRadjBMI (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. |
| first_indexed | 2024-12-13T13:02:24Z |
| format | Article |
| id | doaj.art-ebae43e029a24f359d352325d144406e |
| institution | Directory Open Access Journal |
| issn | 1741-7015 |
| language | English |
| last_indexed | 2024-12-13T13:02:24Z |
| publishDate | 2022-02-01 |
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| spelling | doaj.art-ebae43e029a24f359d352325d144406e2022-12-21T23:44:57ZengBMCBMC Medicine1741-70152022-02-0120111310.1186/s12916-022-02238-yGenomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysisQianwen Liu0Zhaozhong Zhu1Peter Kraft2Qiaolin Deng3Elisabet Stener-Victorin4Xia Jiang5Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska InstitutetDepartment of Emergency Medicine, Massachusetts General Hospital, Harvard Medical SchoolDepartment of Biostatistics, Harvard T.H. Chan School of Public HealthDepartment of Physiology and Pharmacology, Karolinska InstitutetDepartment of Physiology and Pharmacology, Karolinska InstitutetDepartment of Clinical Neuroscience, Center for Molecular Medicine, Karolinska InstitutetAbstract 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 (WHRadjBMI, 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 WHRadjBMI (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 WHRadjBMI 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 WHRadjBMI (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.https://doi.org/10.1186/s12916-022-02238-yPolycystic ovary syndromeObesityBody mass indexFat distributionGenome-wide cross-trait analysis |
| spellingShingle | Qianwen Liu Zhaozhong Zhu Peter Kraft Qiaolin Deng Elisabet Stener-Victorin Xia Jiang Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis BMC Medicine Polycystic ovary syndrome Obesity Body mass index Fat distribution Genome-wide cross-trait analysis |
| title | Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis |
| title_full | Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis |
| title_fullStr | Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis |
| title_full_unstemmed | Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis |
| title_short | Genomic correlation, shared loci, and causal relationship between obesity and polycystic ovary syndrome: a large-scale genome-wide cross-trait analysis |
| title_sort | genomic correlation shared loci and causal relationship between obesity and polycystic ovary syndrome a large scale genome wide cross trait analysis |
| topic | Polycystic ovary syndrome Obesity Body mass index Fat distribution Genome-wide cross-trait analysis |
| url | https://doi.org/10.1186/s12916-022-02238-y |
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