Predicting the development of inflammatory bowel disease (IBD) by combining previously associated environmental and lifestyle factors for the development of an environmental risk score (ERS)

Inflammatory bowel disease (IBD), consisting of ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic, debilitating, relapsing inflammatory disease of the gastrointestinal tract, currently affecting 2.5 million people of European descent. Clinically, UC is characterized by bloody diarrhea and chronic abdominal pain with diffuse mucosal inflammation extending from the anal verge and rectum upwards.6 In contrast, CD is featured with transmural bowel inflammation and can involve any part of gastrointestinal tract, potentially causing fibrotic strictures and (perianal) fistula. Approximately 50% of patients with Crohn’s disease require hospitalization within 10 years after diagnosis. Also, the risk of surgery in UC and CD is still high with rates of approximately 10% and 30%-50%, respectively. Although IBD can occur at any age, most patients are diagnosed at the age of 20-40 years old. Therefore, IBD also created a great economic impact and social burden due to long-term disability and unemployment, with yearly costs estimated around 4.5 billion Euros.7

Disease etiology in IBD is known to be multifactorial with the complex interaction of the genome, microbiome and exposome. Currently, approximately 200 significant genetic loci were identified for IBD. Polygenic risk scores (PRS) have been widely used to estimate the effect of genetic susceptibility on disease risk and outcomes in both candidate gene association studies and genome wide association case-control studies. 8-11 The estimates of heritability of liability for CD and UC, calculated from GWAS, are 0.37 and 0.27, respectively, less than half of the 0.75 and 0.67 from pooled twin studies, indicating limited application of PRS for clinical purposes12. In addition, the “hereditary gap”, difference between the heritability derived from twin studies and GWAS, reflects the potential role of environmental risk factors on the development of IBD.

The exposome describes all exposures to environmental and lifestyle factors starting at conception.13 By introducing the concept of the “hygiene hypothesis”, the impact of early exposures on later life risk was noticed in 1989.14 Also, studies of immigrant populations revealed migration to western countries have a higher risk of developing IBD.15 In addition, increasing prevalence of IBD in newly industrialized regions further supports the critical role played by environment and western lifestyles.16 Recent data revealed numerous environmental- and lifestyle factors associated with an increased or decreased the risk of IBD, ranging from exposures during childhood (i.e. prenatal smoke, breastfeeding and household pets), to potential lifelong exposures (i.e. appendectomy and tonsillectomy). 17,18 However, current studies mainly focus on the effect of single environment risk factors (i.e. smoking, breastfeeding and appendectomy etc.), and do not consider the obvious correlation and interaction among environmental and lifestyle exposures, and thus fail to explain the complex collective effect of exposome on IBD. 

Environmental risk scores (ERS), consisting of previously associated factors, either protective or risk increasing, are a more efficient and accurate approach to quantitatively assess the integrated effect of the exposome in development of IBD. This method was previously used in other diseases, such as childhood asthma, colorectal malignancies and schizophrenia, showing that ERS is a useful tool for measuring environmental triggers and stratifying high risk individuals. 19-21 Furthermore, incorporating a robust ERS not only prevents the disadvantages of hypothesis-driven one exposure/variant studies but also supplements and improves gene-environment interaction studies in which the joint effect of genetic and environmental influences can be comprehensively evaluated. 22-24 Therefore, quantifying cumulative environment risks and their interplay in the development of IBD forms an important next step to gain insight into the etiology of IBD.

year of approval



  • UMCG - Department of Gastroenterology and Hepatology

primary applicant

  • Dijkstra, G.