IBD Risk Factors in Individuals with a Family History
—Some, but not all, first degree relatives of patients with IBD will also be diagnosed with the disorder. Can we identify which family members are at highest risk?
“Having a first-degree relative (FDR) with Crohn's disease or ulcerative colitis is the strongest known risk factor for developing IBD,” Johan Burisch, MD, PhD, told MedPage Today in a recent interview. However, “not everyone with an FDR will eventually develop IBD,” he added.
Dr. Burisch, a gastroenterologist at Hvidovre Hospital, Hvidovre, Denmark, and a clinical epidemiologist at the University of Copenhagen, Denmark was one of the investigators involved in a recent study that examined the associations between non-genetic factors and a future diagnosis of IBD in individuals with a family history to identify those most at risk.1 According to their findings, published in the Journal of Crohn’s and Colitis, female sex, antibiotic exposure, and ankylosing spondylitis are risk factors for future IBD among FDRs of individuals with IBD.1
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Families, cases, and controls
The study included everyone living in Denmark and registered from 1977-2018 in the Danish Civil Registration System. This database contains demographic information starting at birth with linked parental data. These registrations are linked to health data taken from the Danish National Patient Registry, which includes clinical data for all patients discharged from Danish hospitals, and the Danish National Prescription Registry. Diagnoses were determined by ICD-8 or ICD-10 codes in at least 2 National Patient Registry registrations.
To determine biological relatives from the Civil Registration System database, the researchers excluded half-siblings and those individuals with a missing parent on the first registration at birth. The biological parents were the first individuals registered as mother or father.
The study design was case-control with two primary analyses. The first was an analysis of high-risk families with 2 FDRs with IBD. These families had a parent with IBD who had at least 2 children, 1 or more of whom had IBD. Among the children within these families, the investigators compared cases who developed IBD during follow-up and controls who did not.
The second analysis was across families that had 1 member with IBD. Cases were individuals who had a single FDR (parent, child, or sibling) with IBD and who developed IBD during follow-up. Thirty control individuals were matched to each case from among the FDRs who did not develop IBD.
Exposures examined included factors such as patient characteristics, other immune-mediated diseases, gastroenteritis, depression, surgery, or antibiotic use.
Individuals with a parent and sibling with IBD
A total of 1699 families were identified with at least 1 parent, at least 1 child with IBD, and at least 1 child without IBD from among 63,395 patients with IBD. In these families, there were 1732 cases with IBD and 2447 control siblings without IBD.
The investigators found that female sex was significantly associated with higher odds of an IBD diagnosis (adjusted odds ratio [aOR], 1.40; 95% CI, 1.23-1.59) after multivariable conditional logistic regression analysis. IBD was also significantly associated with ankylosing spondylitis (aOR, 2.88; 95% CI, 1.05-7.91).
The odds of a diagnosis of IBD were increased with antibiotic use (aOR, 1.28; 95% CI, 1.02-1.61), particularly broad-spectrum antibiotics (aOR, 1.68; 95% CI, 1.42-2.00).
Individuals with 1 family member with IBD
For the across-family analysis, the investigators identified 1254 cases who developed IBD during follow-up and 37,584 controls among 52,612 individuals who had at least 1 FDR with IBD. In 40.9% of cases and 43.7% of controls, the mother was the affected FDR.
After adjustment for age, sex, follow-up time, relationship to FDR, and the type of IBD of the FDR, the strongest association with the development of IBD was having 3 or more FDRs (aOR, 6.26; 95% CI, 1.34-29.29).
Ankylosing spondylitis and antibiotic use were associated with an increased risk of an IBD diagnosis among family members with a single FDR with IBD. In individuals with ankylosing spondylitis, the adjusted odds of developing IBD was 3.92 (95% CI, 1.38-11.12). The adjusted odds for future IBD were 1.29 (95% CI, 1.04-1.60) for those with a history of antibiotic use and 1.54 (95% CI, 1.35-1.75) for those who used broad-spectrum antibiotics.
Identifying relatives at risk
“We found that in both high-risk families, where both at least 1 parent and at least a child have IBD, as well as in families with only 1 individual having IBD, the risk of another family member developing IBD was increased in females, those with other immune-mediated diseases, such as ankylosing spondylitis, and those exposed to antibiotics,” Dr. Burisch explained.
These findings may “help to identify individuals at higher risk for IBD who could be more intensively monitored for disease development,” said Dr. Burisch. “Ideally, we would like to be able to both identify individuals at risk of developing IBD as well as intervene in a way that reduces or removes this risk,” he added.
Limitations of the study included the inability to account for factors not present in the databases. In addition, the study could have been underpowered to detect associations for some variables. Finally, the investigators could not rule out misclassification in the registries.
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