Genetic risk, lifestyle factors can lead to the onset of IBD in adults

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

In addition, adhering to a healthy lifestyle was associated with an almost 50% lower risk of Crohn’s disease or ulcerative colitis in people at high genetic risk.

“Although the onset of disease in childhood and early adulthood is well recognized, epidemiological studies now highlight an increased incidence and prevalence of IBD onset in midlife or later life,” writes senior author Zoe Lee, from Big Data. in the College of Public Health Sciences. Health at Zhejiang University College of Medicine, Hangzhou, China and colleagues.

“Compared with IBD in children or adolescents, the aetiology of adult IBD is thought to be multifactorial, with both genetic and environmental factors playing important roles in its development,” they wrote.

The study has been published in American Journal of Gastroenterology on January 6th.

Association analysis

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

Lee and colleagues conducted a prospective cohort study based on the UK Biobank to examine 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 recent onset IBD, or with an unclear diagnosis of IBD.

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

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

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

Next, the researchers assigned healthy lifestyle scores, with a higher lifestyle score indicating a higher commitment to a healthy lifestyle. The unweighted outcome was rated as favorable (with four or five healthy lifestyle factors), moderate (with three factors), or unfavorable (with zero to two factors). The study team then created a weighted score and adjusted it for age, gender, education, and other variables. These scores were also rated as favorable, average or unfavorable.

Overall, during the 12-year follow-up, 707 cases of Crohn’s disease and 1,576 cases of ulcerative colitis were diagnosed. The mean age of diagnosis was 65 for Crohn’s and 66 years for ulcerative colitis, both ranging from 43 to 82 years.

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

Overall, a lower healthy lifestyle score was associated with an increased risk of inflammatory bowel disease. With the exception of alcohol consumption, all lifestyle factors have been associated with an increased risk of both Crohn’s and ulcerative colitis.

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

Genetics – Lifestyle Connection

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

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

Across all genetic groups, participants with an unfavorable lifestyle were more likely to develop IBD. For example, among people with low genetic risk, those with an unfavorable lifestyle had a risk ratio of 2.32 for Crohn’s and a risk ratio of 1.7 for ulcerative colitis compared with those with a favorable lifestyle.

In calculating the cumulative risk of IBD over 12 years, individuals with a high genetic risk and an unfavorable lifestyle had a 4.88-fold higher risk or Crohn’s risk and a 5.28-fold higher risk of developing ulcerative colitis than those with a low and favorable genetic risk. lifestyle.

“IBD was once thought to be a disease that is primarily genetically predisposed, but over the years and based on multiple studies, it has been found that the association with IBD and lifestyle/environment play a larger role,” Miguel Reguero, MD, Chief of the division of gastroenterology, said the Institute of Diseases and Surgery at the Cleveland Clinic in Ohio Medscape Medical News.

Regueiro, who was not involved in this study, is looking at the natural course of IBD and postoperative prevention of Crohn’s disease.

case for a healthy lifestyle

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

The findings are “more supportive of a healthy lifestyle,” Reguero said, though the study can’t definitively link lifestyle to cause and effect. “What is even more 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.”

The study authors write that future studies should investigate the effects of lifestyle factors by age, given that this study focused on middle-aged and older populations. In addition, studies should include frequent assessments of lifestyle factors to understand the effects of different periods of time with an unhealthy lifestyle, they wrote.

Reguero noted that Cleveland Clinic has created a medical home for IBD, which focuses on creating a healthy lifestyle, eating a healthy diet, and reducing stress.

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

Am J Gastroenterol. Published online on January 6, 2023. https://doi.org/10.14309/ajg.0000000000002180. Summary

The study was supported by funding from the National Science Fund for Outstanding Young Scientists of Zhejiang Province, the National Natural Science Foundation of China, the Hunan Provincial Research and Development Master Plan, the Swedish Heart and Lung Foundation, the Swedish Research Council, the Swedish Cancer Society, and a CRUK Professional Development Fellowship. The authors and Regueiro declared no relevant financial relationships.

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

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