Evidence mapPaperPMID 30936389Full record

SynthesisThorax2019

Genetic and observational evidence supports a causal role of sex hormones on the development of asthma.

Ryan Arathimos, Raquel Granell, Philip Haycock, Rebecca C Richmond, James Yarmolinsky, Caroline L Relton, Kate Tilling

Open access · hybridAbstract readMeta-Analysis
In one paragraph

Synthesis in Thorax, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
2.9field-weighted citation impact, top 10% 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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Sex Hormones and the Risk of Nasal Polyps: A Two-Sample Mendelian Randomization Study.World journal of otorhinolaryngology - head and neck surgery · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Newborn DNA methylation and asthma acquisition across adolescence and early adulthood.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2022
    Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. The impact of obesity on immune function in pediatric asthma.Current opinion in allergy and clinical immunology · 2021
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Ryan ArathimosPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.ORCID 0000-0002-0473-500X
Raquel GranellPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Philip HaycockPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Rebecca C RichmondPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
James YarmolinskyPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Caroline L ReltonPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Kate TillingPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
University of Bristol · GB

Funding

Medical Research Council G9815508Medical Research Council MC_PC_19009Medical Research Council MC_UU_00011/3Medical Research Council MC_UU_00011/5Medical Research Council MC_UU_12013/2Wellcome TrustWellcome Trust 102215/2/13/2
6 · The paper itself

Abstract

introductionMales have a higher prevalence of asthma in childhood, whereas females have a higher prevalence in adolescence and adulthood. The 'adolescent switch' observed between sexes during puberty has been hypothesised to be due to fluctuating sex hormones. Robust evidence of the involvement of sex hormones in asthma could lead to development of therapeutic interventions.

methodsWe combine observational evidence using longitudinal data on sex hormone-binding globulin (SHBG), total and bioavailable testosterone and asthma from a subset of males (n=512) in the Avon Longitudinal Study of Parents and Children, and genetic evidence of SHBG and asthma using two-sample Mendelian randomisation (MR), a method of causal inference. We meta-analysed two-sample MR results across two large data sets, the Trans-National Asthma Genetics Consortium genome-wide association study of asthma and UK Biobank (over 460 000 individuals combined).

resultsObservational evidence indicated weak evidence of a protective effect of increased circulating testosterone on asthma in males in adolescence, but no strong pattern of association with SHBG. Genetic evidence using two-sample MR indicated a protective effect of increased SHBG, with an OR for asthma of 0.86 (95% CI 0.74 to 1.00) for the inverse-variance weighted approach and an OR of 0.83 (95% CI 0.72 to 0.96) for the weighted median estimator, per unit increase in natural log SHBG. A sex-stratified sensitivity analysis suggested the protective effect of SHBG was mostly evident in females.

conclusionWe report the first suggestive evidence of a protective effect of genetically elevated SHBG on asthma, which may provide a biological explanation behind the observed asthma sex discordance. Further work is required to disentangle the downstream effects of SHBG on asthma and the molecular pathways involved.

Indexed as

AsthmaEvidence-Based MedicineFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyGonadal Steroid HormonesHumansMaleMendelian Randomization AnalysisObservational Studies as TopicSex FactorsSex Hormone-Binding GlobulinTestosteroneTissue BanksGonadal Steroid HormonesSex Hormone-Binding GlobulinTestosteroneALSPACasthmacohortsex hormonesSHBGtestosterone

Identifiers

PMID30936389
PMCPMC6585308
OpenAlexW2903864664

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.