Mendelian randomization indicates causal effects of estradiol levels on kidney function in males
Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function. We conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney functio...
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| Published in: | Frontiers in endocrinology (Lausanne) Vol. 14; p. 1232266 |
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| Main Authors: | , , , |
| Format: | Journal Article |
| Language: | English |
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19.12.2023
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| ISSN: | 1664-2392, 1664-2392 |
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| Abstract | Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.
We conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.
We performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men (
= 206,927) and women (
= 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR,
= 567,460), urine albumin-to-creatinine ratio (UACR,
= 547,361), and CKD (
= 41,395 cases and
= 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data (
= 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.
The two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077;
= 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;
= 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.
We 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. |
|---|---|
| AbstractList | Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function.We conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.ObjectiveWe conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females.We 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.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.The 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.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.We 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.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. Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol, and kidney function. We conducted a Mendelian randomization (MR) study to assess a possible causal effect of estradiol levels on kidney function in males and females. We performed a bidirectional two-sample MR using published genetic associations of serum levels of estradiol in men ( = 206,927) and women ( = 229,966), and of kidney traits represented by estimated glomerular filtration rate (eGFR, = 567,460), urine albumin-to-creatinine ratio (UACR, = 547,361), and CKD ( = 41,395 cases and = 439,303 controls) using data obtained from the CKDGen Consortium. Additionally, we conducted a genome-wide association study using UK Biobank cohort study data ( = 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. The two-sample MR indicated that genetically predicted estradiol levels are significantly associated with eGFR in men (beta = 0.077; = 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; = 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. We 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. 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. |
| Author | Schurmann, Claudia Teumer, Alexander Böttinger, Erwin P. Nasr, M. Kamal |
| AuthorAffiliation | 4 Department of Psychiatry and Psychotherapy, University Medicine Greifswald , Greifswald , Germany 2 Digital Health Center, Hasso Plattner Institute, University of Potsdam , Potsdam , Germany 3 DZHK (German Centre for Cardiovascular Research) , Partner Site Greifswald, Greifswald , Germany 5 Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai , New York, NY , United States 1 Institute for Community Medicine, University Medicine Greifswald , Greifswald , Germany |
| AuthorAffiliation_xml | – name: 1 Institute for Community Medicine, University Medicine Greifswald , Greifswald , Germany – name: 4 Department of Psychiatry and Psychotherapy, University Medicine Greifswald , Greifswald , Germany – name: 2 Digital Health Center, Hasso Plattner Institute, University of Potsdam , Potsdam , Germany – name: 5 Hasso Plattner Institute for Digital Health at Mount Sinai, Icahn School of Medicine at Mount Sinai , New York, NY , United States – name: 3 DZHK (German Centre for Cardiovascular Research) , Partner Site Greifswald, Greifswald , Germany |
| Author_xml | – sequence: 1 givenname: M. Kamal surname: Nasr fullname: Nasr, M. Kamal – sequence: 2 givenname: Claudia surname: Schurmann fullname: Schurmann, Claudia – sequence: 3 givenname: Erwin P. surname: Böttinger fullname: Böttinger, Erwin P. – sequence: 4 givenname: Alexander surname: Teumer fullname: Teumer, Alexander |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/38169598$$D View this record in MEDLINE/PubMed |
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| Keywords | albuminuria steroids glomerular filtration rate genome-wide association study causality |
| Language | English |
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| Snippet | Chronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including estradiol,... ContextChronic kidney disease (CKD) is a public health burden worldwide. Epidemiological studies observed an association between sex hormones, including... |
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| SubjectTerms | albuminuria causality Cohort Studies Endocrinology Estradiol Female Genome-Wide Association Study glomerular filtration rate Humans Kidney Male Mendelian Randomization Analysis Renal Insufficiency, Chronic - etiology Renal Insufficiency, Chronic - genetics steroids |
| Title | Mendelian randomization indicates causal effects of estradiol levels on kidney function in males |
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