Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study
Background: Higher age-specific circulating anti-Müllerian hormone (AMH) levels have been linked to a lower risk of cardiometabolic outcomes. However, whether AMH has a casual role in the etiology of these diseases is unknown. The objective of this study was therefore to explore if circulating AMH l...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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IMR Press
2022-07-01
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| Series: | Reviews in Cardiovascular Medicine |
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| Online Access: | https://www.imrpress.com/journal/RCM/23/8/10.31083/j.rcm2308269 |
| _version_ | 1811283303043432448 |
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| author | Renée M.G. Verdiesen Joanna von Berg M. Abdullah Said Pim van der Harst Anubha Mahajan Carla H. van Gils Yvonne T. van der Schouw N. Charlotte Onland-Moret |
| author_facet | Renée M.G. Verdiesen Joanna von Berg M. Abdullah Said Pim van der Harst Anubha Mahajan Carla H. van Gils Yvonne T. van der Schouw N. Charlotte Onland-Moret |
| author_sort | Renée M.G. Verdiesen |
| collection | DOAJ |
| description | Background: Higher age-specific circulating anti-Müllerian hormone (AMH) levels have been linked to a lower risk of cardiometabolic outcomes. However, whether AMH has a casual role in the etiology of these diseases is unknown. The objective of this study was therefore to explore if circulating AMH levels have a causal effect on risk of coronary artery disease (CAD), ischemic stroke and type 2 diabetes (T2D) in women, using a two-sample Mendelian randomization (MR) approach. Methods: We used four single nucleotide polymorphisms (SNPs) from the most recent AMH GWAS meta-analysis as instrumental variables. Summary-level data for CAD (n = 149,752; 11,802 cases), ischemic stroke (n = 17,541; 4678 cases) and T2D (n = 464,389; 30,052 cases) were extracted from the UK Biobank, the Stroke Genetics Network, and DIAMANTE consortia, respectively. To assess the presence of potential pleiotropy we tested the association of the four AMH SNPs, both individually and combined in a weighted genetic risk score, with a range of cardiovascular risk factors and intermediate traits using UK Biobank data. Results: MR estimates, i.e., inverse variance-weighted odds ratios (ORIVW), did not support a causal effect of circulating AMH levels on CAD (ORIVW = 1.13, 95% CI: 0.95–1.35), ischemic stroke (ORIVW = 1.11, 95% CI: 0.83–1.49), and T2D (ORIVW = 0.98, 95% CI: 0.87–1.10). After adjustment for multiple testing, we observed associations between genetically predicted AMH and age at menopause, and age at menarche, but not with intermediate traits on the causal pathway between AMH and cardiometabolic health, such as atherosclerosis or glucose levels. Conclusions: This study does not provide evidence for a causal effect of circulating AMH levels on CAD, ischemic stroke and T2D in women, although weak instrument bias cannot be excluded. |
| first_indexed | 2024-04-13T02:09:01Z |
| format | Article |
| id | doaj.art-3c35048eac8e492a88bc335ec1326abd |
| institution | Directory Open Access Journal |
| issn | 1530-6550 |
| language | English |
| last_indexed | 2024-04-13T02:09:01Z |
| publishDate | 2022-07-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Reviews in Cardiovascular Medicine |
| spelling | doaj.art-3c35048eac8e492a88bc335ec1326abd2022-12-22T03:07:21ZengIMR PressReviews in Cardiovascular Medicine1530-65502022-07-0123826910.31083/j.rcm2308269S1530-6550(22)00561-0Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization StudyRenée M.G. Verdiesen0Joanna von Berg1M. Abdullah Said2Pim van der Harst3Anubha Mahajan4Carla H. van Gils5Yvonne T. van der Schouw6N. Charlotte Onland-Moret7Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsDivision Laboratory, Pharmacy and Biomedical Genetics, University Medical Center Utrecht, 3584 CX Utrecht, The NetherlandsDepartment of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The NetherlandsDepartment of Cardiology, University Medical Center Groningen, University of Groningen, 9700 RB Groningen, The NetherlandsWellcome Centre for Human Genetics, University of Oxford, OX3 7BN Oxford, UKJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsJulius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, The NetherlandsBackground: Higher age-specific circulating anti-Müllerian hormone (AMH) levels have been linked to a lower risk of cardiometabolic outcomes. However, whether AMH has a casual role in the etiology of these diseases is unknown. The objective of this study was therefore to explore if circulating AMH levels have a causal effect on risk of coronary artery disease (CAD), ischemic stroke and type 2 diabetes (T2D) in women, using a two-sample Mendelian randomization (MR) approach. Methods: We used four single nucleotide polymorphisms (SNPs) from the most recent AMH GWAS meta-analysis as instrumental variables. Summary-level data for CAD (n = 149,752; 11,802 cases), ischemic stroke (n = 17,541; 4678 cases) and T2D (n = 464,389; 30,052 cases) were extracted from the UK Biobank, the Stroke Genetics Network, and DIAMANTE consortia, respectively. To assess the presence of potential pleiotropy we tested the association of the four AMH SNPs, both individually and combined in a weighted genetic risk score, with a range of cardiovascular risk factors and intermediate traits using UK Biobank data. Results: MR estimates, i.e., inverse variance-weighted odds ratios (ORIVW), did not support a causal effect of circulating AMH levels on CAD (ORIVW = 1.13, 95% CI: 0.95–1.35), ischemic stroke (ORIVW = 1.11, 95% CI: 0.83–1.49), and T2D (ORIVW = 0.98, 95% CI: 0.87–1.10). After adjustment for multiple testing, we observed associations between genetically predicted AMH and age at menopause, and age at menarche, but not with intermediate traits on the causal pathway between AMH and cardiometabolic health, such as atherosclerosis or glucose levels. Conclusions: This study does not provide evidence for a causal effect of circulating AMH levels on CAD, ischemic stroke and T2D in women, although weak instrument bias cannot be excluded.https://www.imrpress.com/journal/RCM/23/8/10.31083/j.rcm2308269anti-müllerian hormoneamhcoronary artery diseasestroketype 2 diabetesmendelian randomizationwomen |
| spellingShingle | Renée M.G. Verdiesen Joanna von Berg M. Abdullah Said Pim van der Harst Anubha Mahajan Carla H. van Gils Yvonne T. van der Schouw N. Charlotte Onland-Moret Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study Reviews in Cardiovascular Medicine anti-müllerian hormone amh coronary artery disease stroke type 2 diabetes mendelian randomization women |
| title | Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study |
| title_full | Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study |
| title_fullStr | Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study |
| title_full_unstemmed | Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study |
| title_short | Anti-Müllerian Hormone and Cardiometabolic Disease in Women: A Two-Sample Mendelian Randomization Study |
| title_sort | anti mullerian hormone and cardiometabolic disease in women a two sample mendelian randomization study |
| topic | anti-müllerian hormone amh coronary artery disease stroke type 2 diabetes mendelian randomization women |
| url | https://www.imrpress.com/journal/RCM/23/8/10.31083/j.rcm2308269 |
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