Mendelian randomization indicates causal effects of estradiol levels on kidney function in males
ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1232266/full |
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| author | M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr Claudia Schurmann Erwin P. Böttinger Erwin P. Böttinger Alexander Teumer Alexander Teumer Alexander Teumer |
| author_facet | M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr Claudia Schurmann Erwin P. Böttinger Erwin P. Böttinger Alexander Teumer Alexander Teumer Alexander Teumer |
| author_sort | M. Kamal Nasr |
| collection | DOAJ |
| description | ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.DesignWe performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (n = 206,927) and women (n = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, n = 567,460), urine albumin-to-creatinine ratio (UACR, n = 547,361), and CKD (n = 41,395 cases and n = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (n = 11,798 men and n = 6,835 women) to identify novel genetic associations with levels of estradiol, and then used these variants as instruments in a one-sample MR.ResultsThe two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; p = 5.2E-05). We identified a single locus at chromosome 14 associated with estradiol levels in men being significant in the one-sample MR on eGFR (beta = 0.199; p = 0.017). We revealed significant results with eGFR in postmenopausal women and with UACR in premenopausal women, which did not reach statistical significance in the sensitivity MR analyses. No causal effect of eGFR or UACR on estradiol levels was found.ConclusionsWe conclude that serum estradiol levels may have a causal effect on kidney function. Our MR results provide starting points for studies to develop therapeutic strategies to reduce kidney disease. |
| first_indexed | 2024-03-08T22:02:09Z |
| format | Article |
| id | doaj.art-6f24cced5020468ba2c96dc25ba44b70 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-08T22:02:09Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-6f24cced5020468ba2c96dc25ba44b702023-12-19T11:07:07ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12322661232266Mendelian randomization indicates causal effects of estradiol levels on kidney function in malesM. Kamal Nasr0M. Kamal Nasr1M. Kamal Nasr2M. Kamal Nasr3Claudia Schurmann4Erwin P. Böttinger5Erwin P. Böttinger6Alexander Teumer7Alexander Teumer8Alexander Teumer9Institute for Community Medicine, University Medicine Greifswald, Greifswald, GermanyDigital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, GermanyDigital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, GermanyDigital Health Center, Hasso Plattner Institute, University of Potsdam, Potsdam, GermanyHasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai, New York, NY, United StatesInstitute for Community Medicine, University Medicine Greifswald, Greifswald, GermanyDZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, GermanyDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, GermanyContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.DesignWe performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (n = 206,927) and women (n = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, n = 567,460), urine albumin-to-creatinine ratio (UACR, n = 547,361), and CKD (n = 41,395 cases and n = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (n = 11,798 men and n = 6,835 women) to identify novel genetic associations with levels of estradiol, and then used these variants as instruments in a one-sample MR.ResultsThe two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; p = 5.2E-05). We identified a single locus at chromosome 14 associated with estradiol levels in men being significant in the one-sample MR on eGFR (beta = 0.199; p = 0.017). We revealed significant results with eGFR in postmenopausal women and with UACR in premenopausal women, which did not reach statistical significance in the sensitivity MR analyses. No causal effect of eGFR or UACR on estradiol levels was found.ConclusionsWe conclude that serum estradiol levels may have a causal effect on kidney function. Our MR results provide starting points for studies to develop therapeutic strategies to reduce kidney disease.https://www.frontiersin.org/articles/10.3389/fendo.2023.1232266/fullglomerular filtration ratesteroidsalbuminuriagenome-wide association studycausality |
| spellingShingle | M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr M. Kamal Nasr Claudia Schurmann Erwin P. Böttinger Erwin P. Böttinger Alexander Teumer Alexander Teumer Alexander Teumer Mendelian randomization indicates causal effects of estradiol levels on kidney function in males Frontiers in Endocrinology glomerular filtration rate steroids albuminuria genome-wide association study causality |
| title | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| title_full | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| title_fullStr | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| title_full_unstemmed | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| title_short | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| title_sort | mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
| topic | glomerular filtration rate steroids albuminuria genome-wide association study causality |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1232266/full |
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