BACKGROUND: Metabolic diseases are associated with asthma. While both diseases are heritable, studies on whether family history of metabolic disease predicts asthma and allergy have not been undertaken. We studied whether grand-parents' and parents' cardio-metabolic diseases were associated with asthma and hay fever in the offspring.
METHODS: Asthma phenotypes were studied across three generations using data from the third stage of the RHINE study (2010-11). The 13,499 participants reported information on their own, offsprings' (n=23,649) and parents'(n=26,854) respiratory health. Parents' and grand-parents' metabolic score were defined by latent variables combining stroke, heart disease, hypertension, diabetes and obesity. Associations between parents' and grand-parents' phenotypes (metabolic scores, asthma), and asthma phenotypes in offspring (asthma <10 years, >10 years, hay fever) were estimated using mixed logistic regression and Structural Equation Modeling.
RESULTS: Grandparents' and parents' metabolic score were associated with an increased risk of late-onset asthma (ORgd-mother=1.19, p=.431; ORgd-father=1.75 p=.005; ORparent=1.48 p=.148) and hay fever in offspring (OR=1.30, p=.035; 1.45 p=.001; 0.69 p=.023, respectively), but not with early-onset asthma. Direct effects of grandfather's metabolic score were observed on late asthma and hay fever (β=0.10, p<0.01; β=0.09; p<0.01).
CONCLUSION: This is the first study to show that familial cardio-metabolic disease predicts specific asthma phenotypes and hay fever, independent of familial asthma, suggesting that two distinct pathways carry asthma risk across generations, via familial asthma as well as cardio-metabolic disease.
