Genetic Risk, Lifestyle Factors Can Lead to Adult-Onset IBD

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Genetic risk and modifiable lifestyle factors are independently associated with the risk of developing inflammatory bowel disease (IBD) during adulthood, according to a new report.

Additionally, adhering to a healthy lifestyle was associated with a nearly 50% lower risk of developing Crohn’s disease or ulcerative colitis in those with a high genetic risk.

“Although onset in childhood and early adulthood is well recognized, epidemiological studies now highlight the increasing incidence and prevalence of IBD onset in middle age or later life,” write senior author Xue Li, from the Department of Big Data in Health Science School of Public Health at the Zhejiang University School of Medicine in Hangzhou, China, and colleagues.

“Compared to IBD in children or adolescents, the etiology of adult-onset IBD is believed to be more multifactorial, with genetic and environmental factors playing important roles in its development,” they write.

The study was published in the American Journal of Gastroenterology on January 6.

Analyzing Associations

Although previous studies have identified numerous genetic variants and several modifiable risk factors for IBD, data are limited on the combined effect of genetics and lifestyle, the study authors write.

Li and colleagues conducted a prospective cohort study based on the UK Biobank to examine the associations across genetic risk, modifiable lifestyle factors, and IBD risk. They analyzed data from 453,492 participants recruited between 2006 and 2010, excluding those of non-European ancestry, without genetic information, with new-onset IBD, or with an unclear IBD diagnosis.

The research team constructed a polygenic risk score to estimate the genetic susceptibility to Crohn’s disease or ulcerative colitis using the common genetic variants that were strongly associated with IBD in a previous genome-wide association meta-analysis. They used 51 independent single nucleotide polymorphisms to calculate the risk score for Crohn’s disease and 30 to calculate the risk score for ulcerative colitis.

They also constructed genomic risk scores by including all single nucleotide polymorphisms at a suggestive significance level reported in the genome-wide association study. The research team then either used the polygenic risk score or genomic risk score to represent the genetic susceptibility to IBD and categorized participants into low, intermediate, and high genetic risk groups.

For lifestyle, the research team examined six factors that have been associated with either Crohn’s disease or ulcerative colitis in a recent umbrella review and cohort studies. These factors are smoking, alcohol consumption, obesity, sleep duration, diet, and regular physical activity.

The researchers then constructed healthy lifestyle scores, with a higher lifestyle score indicating higher adherence to a healthy lifestyle. The unweighted score was categorized as favorable (with four or five healthy lifestyle factors), intermediate (with three factors), or unfavorable (with zero to two factors). The study team then created a weighted score and adjusted for age, sex, education, and other variables. These scores also were categorized as favorable, intermediate, or unfavorable.

Overall, during a median follow-up of 12 years, 707 Crohn’s diseases cases and 1576 ulcerative colitis cases were diagnosed. The median age of diagnosis was 65 for Crohn’s and 66 for ulcerative colitis, with both ranging from ages 43 to 82.

For genetic susceptibility, both the polygenic risk and genomic risk scores showed significant associations with the risk for Crohn’s and ulcerative colitis. The risk for IBD increased across the genetic risk categories (from low to high) in a linear fashion. Compared with participants with a low genetic risk, those with a high genetic risk had a 2.24 hazard ratio for Crohn’s and a 2.15 hazard ratio for ulcerative colitis.

In general, a lower healthy lifestyle score was associated with an increased risk for IBD. Except for alcohol consumption, all the lifestyle factors were associated with a higher risk for both Crohn’s and ulcerative colitis.

Additionally, having a healthier lifestyle was significantly associated with a reduced risk for Crohn’s and ulcerative colitis in a dose-response manner. Compared with participants in the favorable category, those in the unfavorable category had a 1.94 hazard ratio for Crohn’s and a 1.98 hazard ratio for ulcerative colitis. The cumulative incidence of IBD during follow-up was higher in the group with an unfavorable lifestyle.

Genetics–Lifestyle Connection

In the joint analysis of genetic risk and healthy lifestyle, the hazard ratios for both Crohn’s and ulcerative colitis showed a linear increase with increasing genetic risk and decreasing healthy lifestyle.

Compared with participants with a low genetic risk and favorable lifestyle, those with a high genetic risk and unfavorable lifestyle had a 4.4 hazard ratio for Crohn’s and 4.44 hazard ratio for ulcerative colitis. There were no significant differences in the hazard ratios between the high genetic risk but favorable lifestyle group and the low genetic risk but unfavorable lifestyle group.

Across all genetic groups, participants with an unfavorable lifestyle had a higher risk for IBD. For instance, among people with a low genetic risk, those with an unfavorable lifestyle had a 2.32 hazard ratio for Crohn’s and 1.7 hazard ratio for ulcerative colitis compared with those with a favorable lifestyle.

In a calculation of cumulative risk for IBD over 12 years, individuals with a high genetic risk and unfavorable lifestyle had a 4.88-times higher risk or Crohn’s and 5.28-times higher risk for ulcerative colitis compared with those who had a low genetic risk and favorable lifestyle.

“IBD was once thought to be a primarily genetically disposed disease, but over the years and based on multiple studies, the association with IBD and lifestyle/environment has been found to play a larger role,” Miguel Regueiro, MD, chair of the Digestive Disease and Surgery Institute at the Cleveland Clinic in Ohio, told Medscape Medical News.

Regueiro, who wasn’t involved with this study, researches the natural course of IBD and postoperative prevention of Crohn’s disease.

Case for Healthy Lifestyle

Li and colleagues note the important clinical implications of promoting a healthy lifestyle as an effective strategy to lower the incidence of IBD, even among those with a high-risk genetic background.

The results “further support a healthy lifestyle,” even though the study can’t conclusively link lifestyle with cause and effect, Regueiro said. “What is most compelling is that if a patient has a strong family history or high genetic risk, eating a healthy diet and living a healthy lifestyle is even more important.”

Future studies should investigate the effects of lifestyle factors by age, given that this study focused on a middle-aged and older population, the study authors write. In addition, studies should include frequently repeated assessments of lifestyle factors to understand the effects of different lengths of time with an unhealthy lifestyle, they write.

The Cleveland Clinic has created an IBD Medical Home, which places an emphasis on creating a healthy lifestyle, eating a healthy diet, and reducing stress, Regueiro noted.

“We are studying the impact of the medical home and lifestyle on IBD,” he said. “As I tell all of my IBD patients and family members of IBD patients, a healthy lifestyle is not only good for preventing cardiovascular disease, but possibly IBD as well.”

Am J Gastroenterol. Published online January 6, 2023. Abstract

The study was supported by funding from the National Science Fund for Distinguished Young Scholars of Zhejiang Province, the National Natural Science Foundation of China, the Key Research and Development Plan of Hunan Province, the Swedish Heart-Lung Foundation, the Swedish Research Council, the Swedish Cancer Society, and the CRUK Career Development Fellowship. The authors and Regueiro declared no relevant financial relationships.

Carolyn Crist is a health and medical journalist who reports on the latest studies for Medscape, MDedge, and WebMD.

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