Familial associations of lung function between parents, offspring and siblings: a two-generation study of the ECRHS and RHINESSA cohorts.

BACKGROUND

The familial aggregation of lung function is incompletely understood, as well as potential sex-specific patterns of associations within families. We aimed to investigate the associations of spirometry measures between parents and offspring and between siblings in two multicentre cohorts.

METHODS

We studied n=1203 parent-offspring pairs and n=254 sibling pairs from the European Community Respiratory Health Survey (parents, mean age 35 years) and Respiratory Health in Northern Europe, Spain and Australia (offspring, mean age 31 years) cohorts. We used multilevel mixed-effect regression models to assess parent-offspring and between-siblings associations of forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) (litres), adjusted for sex, age, height, smoking and body mass index, accounting for clustering within centres and families.

RESULTS

FEV1 and FVC were positively associated between parents and offspring (ß coef. (95% CI): FEV1 0.19 (0.14 to 0.25), FVC 0.19 (0.14 to 0.25)) and between first and second sibling (ß coef. (95% CI): FEV1 0.30 (0.17 to 0.43), FVC 0.20 (0.08 to 0.32)). The associations of FEV1 and FVC between mothers and sons were significantly higher (p<0.05) than the other sex combinations. Between siblings, FEV1 had greater concordance than FVC without evident sex-specific patterns. Results were consistent after exclusion of asthmatic participants. The proportion of variance explained within-family was 76% (95% CI 66% to 87%) for FEV1 and 80% (95% CI 69% to 91%) for FVC, after adjustment for anthropometric factors. The between-family variance was 23% (95% CI 12% to 34%) for FEV1 and 19% (95% CI 8% to 30%) for FVC.

CONCLUSIONS

This study supports phenotypic concordance of lung function within families, with the strongest positive association observed between mothers and sons. Approximately 75-80% of the variance of FEV1 and FVC was explained within-family.