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Asthma
Original research
Plasma adiponectin and risk of asthma: observational analysis, genetic Mendelian randomisation and meta-analysis
  1. Maria Booth Nielsen1,2,3,
  2. Børge G Nordestgaard1,2,3,
  3. Marianne Benn2,3,4,
  4. Yunus Çolak2,5,6
  1. 1 Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
  2. 2 The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
  3. 3 Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  4. 4 Department of Clinical Biochemistry, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
  5. 5 Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen University Hospital, Copenhagen, Denmark
  6. 6 Department of Respiratory Medicine, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark
  1. Correspondence to Dr Yunus Çolak, Department of Respiratory Medicine and the Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark; yunus.colak{at}regionh.dk

Abstract

Background Adiponectin, an adipocyte-secreted protein-hormone with inflammatory properties, has a potentially important role in the development and progression of asthma. Unravelling whether adiponectin is a causal risk factor for asthma is an important issue to clarify as adiponectin could be a potential novel drug target for the treatment of asthma.

Objective We tested the hypothesis that plasma adiponectin is associated observationally and causally (using genetic variants as instrumental variables) with risk of asthma.

Methods In the Copenhagen General Population Study, we did an observational analysis in 28 845 individuals (2278 asthma cases) with plasma adiponectin measurements, and a genetic one-sample Mendelian randomisation analysis in 94 868 individuals (7128 asthma cases) with 4 genetic variants. Furthermore, in the UK Biobank, we did a genetic two-sample Mendelian randomisation analysis in 462 933 individuals (53 598 asthma cases) with 12 genetic variants. Lastly, we meta-analysed the genetic findings.

Results While a 1 unit log-transformed higher plasma adiponectin in the Copenhagen General Population Study was associated with an observational OR of 1.65 (95% CI 1.29 to 2.08) for asthma, the corresponding genetic causal OR was 1.03 (95% CI 0.75 to 1.42). The genetic causal OR for asthma in the UK Biobank was 1.00 (95% CI 0.99 to 1.00). Lastly, genetic meta-analysis confirmed lack of association between genetically high plasma adiponectin and causal OR for asthma.

Conclusion Observationally, high plasma adiponectin is associated with increased risk of asthma; however, genetic evidence could not support a causal association between plasma adiponectin and asthma.

  • asthma
  • asthma genetics
  • asthma epidemiology

Data availability statement

Data are available on reasonable request. Data from the Copenhagen General Population Study can be made locally accessible under controlled conditions from the corresponding author upon reasonable request.For two-sample Mendelian randomisation analysis data are available through the MR-Base platform for two-sample Mendelian randomisation using summary data from the GWAS Catalog. In the present study we used data on plasma adiponectin from the ADIPOGen(id:ieu-a-1) and (1) asthma doctor diagnosis (UK Biobank id: ukb-b-11297), (2) self-reported asthma (ukb-b-18113) and (3) asthma hospital admission (ukb-d-ASTHMA_HOSPITAL1).

https://doi.org/10.1136/thoraxjnl-2021-217675

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    Data availability statement

    Data are available on reasonable request. Data from the Copenhagen General Population Study can be made locally accessible under controlled conditions from the corresponding author upon reasonable request.For two-sample Mendelian randomisation analysis data are available through the MR-Base platform for two-sample Mendelian randomisation using summary data from the GWAS Catalog. In the present study we used data on plasma adiponectin from the ADIPOGen(id:ieu-a-1) and (1) asthma doctor diagnosis (UK Biobank id: ukb-b-11297), (2) self-reported asthma (ukb-b-18113) and (3) asthma hospital admission (ukb-d-ASTHMA_HOSPITAL1).

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    Footnotes

    • Contributors MBN and YÇ had full access to all data in the study and had final responsibility for the decision to submit for publication. MBN, BGN, MB and YÇ contributed to the study concept and design. MBN, BGN, MB and YÇ collected, analysed or interpreted the data. MBN wrote the draft manuscript. MBN and YÇ did the statistical analyses. MBN, BGN, MB and YÇ revised the manuscript for important intellectual content. BGN and MBN obtained funding. BGN provided administrative, technical and material support. MB, BGN and YÇ supervised the study. YÇ is the guarantor of the article.

    • Funding MBN and BGN were supported by the Research Foundation for Health Research of the Capital Region of Denmark, and MBN by Director Kurt Bønnelycke and Mrs. Grethe Bønnelycke Foundation.

    • Disclaimer The funding sources were not involved in the conduct of research or preparation of the article.

    • Competing interests MBN, MB and BGN have nothing to disclose. YÇ reports personal fees from Boehringer Ingelheim, AstraZeneca and Sanofi Genzyme outside the submitted work.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.