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. © 2010 The Authors Annals of Human Genetics

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Annals of Human Genetics
Erasmus MC: University Medical Center Rotterdam

Lee, J., Essers, J., Kugathasan, S., Escher, J., Lettre, G., Butler, J., … Hirschhorn, J. (2010). Association of Linear Growth Impairment in Pediatric Crohn's Disease and a Known Height Locus: A Pilot Study. Annals of Human Genetics, 74(6), 489–497. doi:10.1111/j.1469-1809.2010.00606.x