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Am J Clin Nutr. 2012 Dec;96(6):1299-308. doi: 10.3945/ajcn.112.043406. Epub 2012 Nov 7.

Genetic modifiers of nutritional status in cystic fibrosis.

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1
Department of Pediatrics and McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA.

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-z(5to10)). The genetic contribution to the variation in BMI-z(5to10) (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-z(5to10) 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-z(5to10) 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.

PMID:
23134884
PMCID:
PMC3497925
DOI:
10.3945/ajcn.112.043406
[Indexed for MEDLINE]
Free PMC Article
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