title: Body Mass Index, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohn's Disease.
abstract: BACKGROUND
  Obesity is associated with systemic and intestine-specific inflammation and alterations in gut microbiota, which in turn impact mucosal immunity. Nonetheless, a specific role of obesity and its interaction with genetics in the progression of Crohn's disease (CD) is unclear.
  
  
  METHODS
  We conducted a cross-sectional study of patients with CD enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. A genetic risk score was calculated using previously reported single-nucleotide polymorphisms-associated genome-wide with CD susceptibility. We used logistic regression to estimate the effect of body mass index (BMI) and its interaction with genetic risk on risk of CD complications.
  
  
  RESULTS
  Among 846 patients with CD, 350 required surgery, 242 with penetrating disease, 182 with stricturing disease, and 226 with perianal disease. There were no associations between obesity (BMI ≥ 30 kg/m2) and risk of perianal disease, stricturing disease, or surgery. Compared with normal-weight individuals with BMI < 25 kg/m2, obesity was associated with lower risk of penetrating disease (odds ratio [OR = 0.56; 95% confidence interval [CI], 0.31-0.99). This association persists among a subgroup of participants with available BMI before development of penetrating disease (OR = 0.40; 95% CI, 0.16-0.88). There were no interactions between BMI and genetic risk score on risk of CD complications (all P interaction > 0.28).
  
  
  CONCLUSIONS
  Our data suggest that obesity does not negatively impact long-term progression of CD, even after accounting for genetic predisposition.
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Pringle
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Kathleen O
authors.initials: KO
authors.lastname: Stewart
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Peloquin
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Holly C
authors.initials: HC
authors.lastname: Sturgeon
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Deanna
authors.initials: D
authors.lastname: Nguyen
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Jenny
authors.initials: J
authors.lastname: Sauk
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: John J
authors.initials: JJ
authors.lastname: Garber
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Vijay
authors.initials: V
authors.lastname: Yajnik
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Ashwin N
authors.initials: AN
authors.lastname: Ananthakrishnan
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.|Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Chan
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.|The Broad Institute, Cambridge, MA 02124.|Center for Computational & Integrative Biology, Massachusetts General Hospital, Boston MA 02114.
authors.forename: Ramnik J
authors.initials: RJ
authors.lastname: Xavier
authors.affiliation: Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114.
authors.forename: Hamed
authors.initials: H
authors.lastname: Khalili
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015992:Body Mass Index; D003251:Constriction, Pathologic / Q000209:etiology; D003424:Crohn Disease / Q000150:complications* / Q000235:genetics* / Q000473:pathology; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012042:Registries; D012307:Risk Factors; D055815:Young Adult