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J Crohns Colitis. 2016 Feb;10(2):209-15. doi: 10.1093/ecco-jcc/jjv197. Epub 2015 Oct 28.

IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn's Disease Patients.

Author information

1
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
2
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada.
3
Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, The Hospital for Sick Children, Toronto, ON, Canada.
4
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
5
The Hospital for Sick Children Research Institute, The Hospital for Sick Children, Toronto, ON, Canada.
6
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada Institute of Medical Science, University of Toronto, Toronto, ON, Canada Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
7
Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital, Toronto, ON, Canada Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada KCroitoru@mtsinai.on.ca.

Abstract

BACKGROUND:

Family history provides important information on risk of developing inflammatory bowel disease [IBD], and genetic profiling of first-degree relatives [FDR] of Crohn's disease [CD]- affected individuals might provide additional information. We aimed to delineate the genetic contribution to the increased IBD susceptibility observed in FDR.

METHODS:

N = 976 Caucasian, healthy, non-related FDR; n = 4997 independent CD; and n = 5000 healthy controls [HC]; were studied. Genotyping for 158 IBD-associated single nucleotide polymorphisms [SNPs] was performed using the Illumina Immunochip. Risk allele frequency [RAF] differences between FDR and HC cohorts were correlated with those between CD and HC cohorts. CD and IBD genetic risk scores [GRS] were calculated and compared between HC, FDR, and CD cohorts.

RESULTS:

IBD-associated SNP RAF differences in FDR and HC cohorts were strongly correlated with those in CD and HC cohorts, correlation coefficient 0.63 (95% confidence interval [CI] 0.53 - 0.72), p = 9.90 x 10(-19). There was a significant increase in CD-GRS [mean] comparing HC, FDR, and CD cohorts: 0.0244, 0.0250, and 0.0257 respectively [p < 1.00 x 10(-7) for each comparison]. There was no significant difference in the IBD-GRS between HC and FDR cohorts [p = 0.81]; however, IBD-GRS was significantly higher in CD compared with FDR and HC cohorts [p < 1.00 x 10(-10) for each comparison].

CONCLUSION:

FDR of CD-affected individuals are enriched with IBD risk alleles compared with HC. Cumulative CD-specific genetic risk is increased in FDR compared with HC. Prospective studies are required to determine if genotyping would facilitate better risk stratification of FDR.

KEYWORDS:

Crohn’s disease; first-degree relatives; genotyping

PMID:
26512135
PMCID:
PMC5007582
DOI:
10.1093/ecco-jcc/jjv197
[Indexed for MEDLINE]
Free PMC Article

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