Evidence map›Paper›PMID 33705547›Full record

ArticleThe Journal of clinical endocrinology and metabolism2021

Association of Genetically Predicted Serum Estradiol With Risk of Thromboembolism in Men: A Mendelian Randomization Study.

Maria Nethander, Johan Quester, Liesbeth Vandenput, Claes Ohlsson

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

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. Cited by 7 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 2 pooled it
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Maria NethanderCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.ORCID 0000-0003-3688-906X
Johan QuesterCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.
Liesbeth VandenputCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-1712-6131
Claes OhlssonCentre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, SE-413 45 Gothenburg, Sweden.ORCID 0000-0002-9633-2805
Sahlgrenska University Hospital · SEUniversity of Gothenburg · SE

Funding

Medical Research Council MC_PC_17228Medical Research Council MC_QA137853
6 · The paper itself

Abstract

contextAn association was recently reported between genetic markers related to high testosterone and increased risk of thromboembolism in men, but a possible causal role of estradiol for risk of thromboembolism in men remains unknown.

objectiveThis work aimed to determine whether endogenous estradiol has a causal role in thromboembolism in men.

methodsA 2-sample mendelian randomization study using gene-based genetic instruments assessed the association between endogenous estradiol genetically predicted by 22 variants in the aromatase CYP19A1 gene region and the risk of thromboembolism (5815 cases) in 170 593 unrelated men of White ancestry in the UK Biobank. The main outcome measure included thromboembolism based on self-reports, hospital episodes, and death.

resultsEndogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of thromboembolism (odds ratio per SD increase in estradiol 0.74; 95% CI, 0.62-0.90). In contrast, genetic variants in the JMJD1C gene, used as a predictor of high endogenous testosterone, were associated with an increased risk of thromboembolism (odds ratio per SD increase in testosterone 1.39; 95% CI, 1.12-1.72). Subsequent explorative analyses evaluating potential repercussions of thromboembolism revealed that endogenous estradiol genetically predicted by variants in the CYP19A1 gene region was inversely associated with the risk of ischemic stroke (0.68; 95% CI, 0.49-0.95) but not myocardial infarction (0.97; 95% CI, 0.84-1.13).

conclusionGenetically predicted estradiol was inversely associated with the risk of thromboembolism and ischemic stroke in men. The ratio between testosterone and estradiol, determined by CYP19A1 activity, may contribute to the overall impact of sex steroids on thromboembolism in men.

Indexed as

Polymorphism, Single NucleotideAgedAromataseEstradiolGenetic Association StudiesHumansMaleMendelian Randomization AnalysisMiddle AgedTestosteroneThromboembolismAromataseCYP19A1 protein, humanEstradiolTestosteronearomataseestradiolmendelian randomizationtestosteronethromboembolism

Identifiers

PMID33705547
PMCPMC8277207
OpenAlexW3133815342

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.