Plasma adiponectin and risk of asthma: observational analysis, genetic Mendelian randomisation and meta-analysis

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.