Association of linear growth impairment in pediatric Crohn's disease and a known height locus: a pilot study

Ann Hum Genet. 2010 Nov;74(6):489-97. doi: 10.1111/j.1469-1809.2010.00606.x. Epub 2010 Sep 15.


The etiology of growth impairment in Crohn's disease (CD) has been inadequately explained by nutritional, hormonal, and/or disease-related factors, suggesting that genetics may be an additional contributor. The aim of this cross-sectional study was to investigate genetic variants associated with linear growth in pediatric-onset CD. We genotyped 951 subjects (317 CD patient-parent trios) for 64 polymorphisms within 14 CD-susceptibility and 23 stature-associated loci. Patient height-for-age Z-score < -1.64 was used to dichotomize probands into growth-impaired and nongrowth-impaired groups. The transmission disequilibrium test (TDT) was used to study association to growth impairment. There was a significant association between growth impairment in CD (height-for-age Z-score < -1.64) and a stature-related polymorphism in the dymeclin gene DYM (rs8099594) (OR = 3.2, CI [1.57-6.51], p = 0.0007). In addition, there was nominal over-transmission of two CD-susceptibility alleles, 10q21.1 intergenic region (rs10761659) and ATG16L1 (rs10210302), in growth-impaired CD children (OR = 2.36, CI [1.26-4.41] p = 0.0056 and OR = 2.45, CI [1.22-4.95] p = 0.0094, respectively). Our data indicate that genetic influences due to stature-associated and possibly CD risk alleles may predispose CD patients to alterations in linear growth. This is the first report of a link between a stature-associated locus and growth impairment in CD.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Body Height / genetics*
  • Child
  • Child, Preschool
  • Crohn Disease / genetics
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Growth Disorders / etiology*
  • Growth Disorders / genetics
  • Humans
  • Infant
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Pilot Projects
  • Proteins / metabolism
  • White People


  • DYM protein, human
  • Intracellular Signaling Peptides and Proteins
  • Proteins

Supplementary concepts

  • Pediatric Crohn's disease