Difference in clinical course, genetics, and the microbiome between familial and sporadic inflammatory bowel diseases

Borren NZ1,2, Conway G1, Garber JJ1,2, Khalili H1,2, Budree S3, Mallick H4, Yajnik V1,2, Xavier RJ1,2, Ananthakrishnan AN1,2. J Crohns Colitis. 2017 Nov 14. doi: 10.1093/ecco-jcc/jjx154. [Epub ahead of print]
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1 Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA.

2 Harvard Medical School, Boston, MA, USA.

3 The University of Capetown, Cape Town, South Africa; OpenBiome, Cambridge, MA; The Discovery Foundation, South Africa.

4 Department of Biostatistics, Harvard T.H. Chan School of Public Health.


OBJECTIVE: Family history is the strongest risk factor for developing Crohn's disease (CD) or ulcerative colitis (UC). We investigated whether the proximity of relationship with the affected relative and concordance for type of IBD modifies the effect of family history on phenotype and disease severity.

DESIGN: This cross-sectional study included patients with a confirmed diagnosis of IBD in a clinical registry. Family history of IBD was assessed by a questionnaire ascertaining presence of disease in a 1 st degree, 2 nd degree or a distant relative. Our primary outcomes were disease phenotype per the Montreal classification and severity measured by need for immunomodulator, biologic, or surgical therapy. Genotyping was performed on the Immunochip and fecal samples subjected to 16s rRNA microbiome sequencing.

RESULTS: Our study included 2,136 patients with IBD (1,197 CD, 939 UC). Just under one-third (32%) were familial IBD (17% 1 st degree, 21% 2 nd degree). Familial IBD was diagnosed at an earlier age, both in CD (26 vs. 28 years, p=0.0006) and UC (29 vs. 32 years, p=0.01). Among CD patients, a positive family history for CD was associated with an increased risk for complicated disease in the presence of an affected family member (OR 1.48, 95% CI 1.07 - 2.03). However, this effect was significant only for 1 st degree relative (OR 1.82, 95% CI 1.19 - 2.78).

CONCLUSION: A family history of CD in 1st degree relatives was associated with complicated CD. Family history discordant for type of IBD or in distant relatives did not influence disease phenotype or natural history.

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