Genetic potential and height velocity during childhood and adolescence do not fully account for shorter stature in cystic fibrosis.

Abstract

Background:Despite improved health, shorter stature is common in cystic fibrosis (CF). We aimed to describe height velocity (HV) and contribution of height-related genetic variants to height(HT) in CF.Methods:HV cohort –Standard deviation scores (-Z) for HT, mid-parental height-adjusted HT (MPAH), and HV were generated using our Pediatric Center’s CF Foundation registry data. HV-Z was compared to population means at each age (5–17y), the relationship of HV-Z with HT-Z assessed, and HT-Z compared to MPAH-Z.GRS cohort-HT genetic risk-Z (HT-GRS-Z) were determined for pancreatic exocrine sufficient (PS) and insufficient (PI) youth and adults from our CF center and their relationships with HT-Z assessed.Results:HV cohort:Average HV-Z was normal across ages in our cohort but was 1.5x-lower (p<0.01) for each SD decrease in HT-Z. MPAH-Z was lower than HT-Z (p< 0.001).GRS cohort:HT-GRS-Z more strongly correlated with HT-Z and better explained height variance in PS (rho=0.42;R2=0.25) vs. PI (rho=0.27;R2=0.11).Conclusions:Despite shorter stature compared to peers and mid-parental height, youth with CF generally have normal linear growth in mid- and late-childhood. PI tempered the heritability of height. These results suggest that, in CF, final height is determined early in life in CF and genetic potential is attenuated by other factors.