Plasma adiponectin and risk of asthma: observational and Mendelian randomization studies in up to 557,801 individuals

Abstract

Objective: Adiponectin is a protein-hormone with anti-inflammatory properties secreted by adipocytes. We tested the hypothesis that plasma adiponectin is causally associated with risk of asthma.

Methods: Information on 94,868 individuals from the Copenhagen General Population Study was used in observational and one-sample Mendelian analyses, using 4 genetic variants for plasma adiponectin. Asthma diagnosis was ascertained through self-report, hospital contacts, and medical treatment. Findings were validated in a two-sample Mendelian design with 462,933 individuals from the UK Biobank, including 53,598 with asthma, using 14 genetic variants from the ADIPOGen consortium.

Results: In observational analyses, 2,278 had asthma among 28,845 individuals, and 7,128 among 94,868 individuals in one-sample Mendelian analyses. Observationally, and compared to individuals with median plasma adiponectin of 10 µg/mL (1st tertile), multivariable adjusted odds ratios for asthma were 1.04(95% confidence interval: 0.92-1.17) for 16.4 µg/mL (2nd tertile) and 1.18(1.03-1.36) for 26.3 µg/mL (3rd tertile). Causal genetically, no association was observed between plasma adiponectin and risk of asthma. A 1 µg/mL higher plasma adiponectin was associated with an observational odds ratio of 1.02(1.01-1.02) for asthma, but a genetically determined causal risk ratio of 1.00(0.98-1.02) for asthma. Summary-level data from the UK Biobank and ADIPOGen consortium gave a causal risk ratio of 1.00(0.99-1.00) for asthma.

Conclusion: Observationally, high plasma adiponectin is associated with increased risk of asthma; however, genetically, plasma adiponectin is not causally associated with risk of asthma.