Genetic modifiers of nutritional status in cystic fibrosis

Gia M. Bradley, Scott M. Blackman, Christopher P. Watson, Vishal K. Doshi, Garry R. Cutting

Research output: Contribution to journalArticle

Abstract

Background: Improved nutrition early in life is associated with better pulmonary function for patients with cystic fibrosis (CF). However, nutritional status is poorly correlated with the CFTR genotype. Objective: We investigated the extent to which modifier genes influence nutrition in children with CF. Design: BMI data were longitudinally collected from the CF Twin-Sibling Study and Cystic Fibrosis Foundation Patient Registry for twins and siblings from 2000 to 2010. A nutritional phenotype was derived for 1124 subjects by calculating the average BMI z score from 5-10 y of age (BMI-z5to10). The genetic contribution to the variation in BMI-z5to10 (ie, heritability) was estimated by comparing the similarity of the phenotype in monozygous twins to that in dizygous twins and siblings. Linkage analysis identified potential modifier-gene loci. Results: The median BMI-z5to10 was -0.07 (range: -3.89 to 2.30), which corresponded to the 47th CDC percentile. BMI-z 5to10 was negatively correlated with pancreatic insufficiency, history of meconium ileus, and female sex but positively correlated with later birth cohorts and lung function. Monozygous twins showed greater concordance for BMI-z5to10 than did dizygous twins and siblings; heritability estimates from same-sex twin-only analyses ranged from 0.54 to 0.82. For 1010 subjects with pancreatic insufficiency, genome-wide significant linkage was identified on chromosomes 1p36.1 [log of odds (LOD): 5.3] and 5q14 (LOD: 5.1). These loci explained ≥16% and ≥15%, respectively, of the BMI variance. Conclusions: The analysis of twins and siblings with CF indicates a prominent role for genes other than CFTR to BMI variation. Specifically, regions on chromosomes 1 and 5 appear to harbor genetic modifiers of substantial effect.

Original languageEnglish (US)
Pages (from-to)1299-1308
Number of pages10
JournalAmerican Journal of Clinical Nutrition
Volume96
Issue number6
DOIs
StatePublished - Dec 1 2012

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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