ArticleThe Journal of clinical endocrinology and metabolism2021
Genome-wide Association Study of Estradiol Levels and the Causal Effect of Estradiol on Bone Mineral Density.
Article in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 56 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 4 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Genome-wide meta-analysis identifies genetic drivers of bile acid metabolism in intrahepatic cholestasis of pregnancy.Nature communications · 2026Pooled it
- Sex hormones and reproductive factors with cardiac arrhythmia and ECG indices: a mendelian randomization study.BMC cardiovascular disorders · 2024Pooled it
- Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.BMC endocrine disorders · 2024Pooled it
- Osteoporosis and Primary Biliary Cholangitis: A Trans-ethnic Mendelian Randomization Analysis.Clinical reviews in allergy & immunology · 2024Pooled it
- Exploring the Causal Relationship Between Sex Hormones and Depression by Means of Two-Sample Mendelian Randomization Analysis.Actas espanolas de psiquiatria · 2026Article
- Article
- Causal effect heterogeneity estimation using summary statistics.Research square · 2026Article
- Genetic Association Between Sex Hormones, Serum Urate, and Gout: A Comprehensive Mendelian Randomization Study.International journal of endocrinology · 2026Article
- Evaluating the causal relationship between sex hormones and oral cavity cancer: a Mendelian randomization study.Archives of medical science : AMS · 2026Article
- The Leucine-mTOR-Autophagy Axis in Granulosa Cells Mediates Circadian Disruption-Induced Anovulation.International journal of biological sciences · 2026Article
- Association of female reproductive traits with altered aging trajectories: Insights from genetic and observational analyses.Cell reports. Medicine · 2025Observational
- No causal links between estradiol and female's brain and mental health using Mendelian randomization.Nature communications · 2025Article
- Association of ABO Blood Groups with Osteoporotic Hip Fracture Susceptibility in Chinese Adults.Calcified tissue international · 2025Article
- Improving accuracy in genome-wide association studies: a two-step approach for handling below limit of detection biomarker measurements.NAR genomics and bioinformatics · 2025Article
- Associations between sex hormones and obesity-related indicators: results from the NHANES and Mendelian randomization study.European journal of medical research · 2025Article
- Effect Modification by Levels of Sex Hormones in the Association between Adiposity and Cancer Incidence in the UK Biobank.Cancer prevention research (Philadelphia, Pa.) · 2025Article
- Independent effects of mental health disorders on breast cancer and their mediating factors: evidence from NHANES and two-step Mendelian randomization.Discover oncology · 2025Article
- Association between estrogen and kidney function: population based evidence and mutual bidirectional Mendelian randomization study.Clinical and experimental nephrology · 2025Article
- The association between sex hormones and bone mineral density in US females.Scientific reports · 2025Article
- Exploring estrogen-related mechanisms in ovarian carcinogenesis: association between bone mineral density and ovarian cancer risk in a multivariable Mendelian randomization study.Cancer causes & control : CCC · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
contextEstradiol is the primary female sex hormone and plays an important role for skeletal health in both sexes. Several enzymes are involved in estradiol metabolism, but few genome-wide association studies (GWAS) have been performed to characterize the genetic contribution to variation in estrogen levels.
objectiveIdentify genetic loci affecting estradiol levels and estimate causal effect of estradiol on bone mineral density (BMD).
designWe performed GWAS for estradiol in males (n = 147 690) and females (n = 163 985) from UK Biobank. Estradiol was analyzed as a binary phenotype above/below detection limit (175 pmol/L). We further estimated the causal effect of estradiol on BMD using Mendelian randomization.
resultsWe identified 14 independent loci associated (P < 5 × 10-8) with estradiol levels in males, of which 1 (CYP3A7) was genome-wide and 7 nominally (P < 0.05) significant in females. In addition, 1 female-specific locus was identified. Most loci contain functionally relevant genes that have not been discussed in relation to estradiol levels in previous GWAS (eg, SRD5A2, which encodes a steroid 5-alpha reductase that is involved in processing androgens, and UGT3A1 and UGT2B7, which encode enzymes likely to be involved in estradiol elimination). The allele that tags the O blood group at the ABO locus was associated with higher estradiol levels. We identified a causal effect of high estradiol levels on increased BMD in both males (P = 1.58 × 10-11) and females (P = 7.48 × 10-6).
conclusionOur findings further support the importance of the body's own estrogen to maintain skeletal health in males and in females.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.