Nienke Z Borren1,2, Grace Conway1, John J Garber1,2, Hamed Khalili1,2, Shrish Budree3, Himel Mallick4, Vijay Yajnik1,2, Ramnik J Xavier1,2, Ashwin N Ananthakrishnan1,2. 1. Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA. 2. Harvard Medical School, Boston, MA, USA. 3. Department of Pediatrics, University of Cape Town, Cape Town, South Africa; OpenBiome, Cambridge, MA, USA; The Discovery Foundation, Johannesburg, South Africa. 4. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Abstract
BACKGROUND AND AIM: 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 inflammatory bowel disease [IBD] modifies the effect of family history on phenotype and disease severity. METHOD: 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 first-first-degree, second-second-degree or distant relative. Our primary outcomes were disease phenotype as per the Montreal classification and severity measured by need for immunomodulator, biologic, or surgical therapy. Genotyping was performed on the Immunochip and faecal samples were subjected to 16S rRNA microbiome sequencing. RESULTS: Our study included 2136 patients with IBD [1197 CD, 939 UC]. Just under one-third [32%] of cases ere familial IBD [17% first-degree, 21% second-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 (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.07-2.03). However, this effect was significant only for first-degree relatives [OR 1.82, 95% CI 1.19-2.78]. CONCLUSIONS: A family history of CD in first-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.
BACKGROUND AND AIM: 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 inflammatory bowel disease [IBD] modifies the effect of family history on phenotype and disease severity. METHOD: 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 first-first-degree, second-second-degree or distant relative. Our primary outcomes were disease phenotype as per the Montreal classification and severity measured by need for immunomodulator, biologic, or surgical therapy. Genotyping was performed on the Immunochip and faecal samples were subjected to 16S rRNA microbiome sequencing. RESULTS: Our study included 2136 patients with IBD [1197 CD, 939 UC]. Just under one-third [32%] of cases ere familial IBD [17% first-degree, 21% second-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 (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.07-2.03). However, this effect was significant only for first-degree relatives [OR 1.82, 95% CI 1.19-2.78]. CONCLUSIONS: A family history of CD in first-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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