The Promise of Polygenic Risk Scores as a Research Tool to Analyse the Genetics Underlying IBD Phenotypes

Abakkouy, Yasmina; Cleynen, Isabelle

doi:10.1093/ecco-jcc/jjab021

Cited by 3 publications

(2 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Polygenic risk scores provide a means to aggregate the genes implicated in Crohn’s disease to then potentially predict the likelihood of an individual developing the disease [ 48 ]. Acknowledging the diverse ethnic populations affected by Crohn’s disease and the variability in their respective implicated genetic loci, a recent study combined polygenic risk scores from European, African-American and Ashkenazi Jewish reference case-control studies to successfully improve the prediction of disease in these cohorts [ 49 ]. Another study, which evaluated the polygenic risk scores of two independent IBD cohorts, found an association between the composite genetic risk of Crohn’s and fibrostenotic disease, even after the exclusion of NOD2, MHC and MST1 [ 50 ].…”

Section: Genomicsmentioning

confidence: 99%

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Kamal,

Parkash,

Beattie

et al. 2023

JCM

View full text Add to dashboard Cite

Crohn’s disease (CD) is a type of inflammatory bowel disease. The number of IBD cases worldwide was estimated to be 4.9 million in 2019. CD exhibits heterogeneity in clinical presentation, anatomical involvement, disease behaviour, clinical course and response to treatment. The classical description of CD involves transmural inflammation with skip lesions anywhere along the entire gastrointestinal tract. The complexity and heterogeneity of Crohn’s disease is not currently reflected in the conventional classification system. Though the knowledge of Crohn’s pathophysiology remains far from understood, the established complex interplay of the omics—genomics, transcriptomics, proteomics, epigenomics, metagenomics, metabolomics, lipidomics and immunophenomics—provides numerous targets for potential molecular markers of disease. Advancing technology has enabled identification of small molecules within these omics, which can be extrapolated to differentiate types of Crohn’s disease. The multi-omic future of Crohn’s disease is promising, with potential for advancements in understanding of its pathogenesis and implementation of personalised medicine.

show abstract

Section: Genomicsmentioning

confidence: 99%

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Kamal,

Parkash,

Beattie

et al. 2023

JCM

View full text Add to dashboard Cite

show abstract

“…Individuals predisposed to UC could benefit from a predictive model that alerts them to their disease risk and enables them to take early steps to reduce this risk. Given the stability of genetic markers, the polygenic risk score (PRS) derived from summary statistics of genome-wide association studies (GWAS) is a promising tool for inferring an individual’s genetic risk for complex diseases [ 6 , 7 ]. PRS has proven effective in predicting diseases such as prostate cancer and coronary heart disease [ 8 , 9 , 10 ]; however, its application in UC remains limited, which highlights substantial opportunities for further research.…”

Section: Introductionmentioning

confidence: 99%

A Polygenic Risk Analysis for Identifying Ulcerative Colitis Patients with European Ancestry

Liu,

Wu,

et al. 2024

Genes

View full text Add to dashboard Cite

The incidence of ulcerative colitis (UC) has increased globally. As a complex disease, the genetic predisposition for UC could be estimated by the polygenic risk score (PRS), which aggregates the effects of a large number of genetic variants in a single quantity and shows promise in identifying individuals at higher lifetime risk of UC. Here, based on a cohort of 2869 UC cases and 2900 controls with genotype array datasets, we used PRSice-2 to calculate PRS, and systematically analyzed factors that could affect the power of PRS, including GWAS summary statistics, population stratification, and impact of variants. After leveraging a stepwise condition analysis, we eventually established the best PRS model, achieving an AUC of 0.713. Meanwhile, samples in the top 20% of the PRS distribution had a risk of UC more than ten times higher than samples in the lowest 20% (OR = 10.435, 95% CI 8.571–12.703). Our analyses demonstrated that including population-enriched, more disease-associated SNPs and using GWAS summary statistics from similar ethnic background can improve the power of PRS. Strictly following the principle of focusing on one population in all aspects of generating PRS can be a cost-effective way to apply genotype-array-derived PRS to practical risk estimation.

show abstract

Enhanced Risk of Gastroesophageal Reflux Disease and Esophageal Complications in the Ulcerative Colitis Population

Wang,

Almetwali,

Wang

et al. 2024

JCM

View full text Add to dashboard Cite

Background: Although heartburn and reflux are frequently reported in ulcerative colitis [UC], the correlation between UC and gastroesophageal reflux disease [GERD], and its complications, esophageal stricture and Barrett’s esophagus [BE], is not well understood. This study aims to examine the prevalence and associated risk of GERD and its complications within the UC population. Methods: We analyzed the National Inpatient Sample (NIS) dataset, consisting of 7,159,694 patients, comparing GERD patients with and without UC to those without GERD. We assessed the degree of colonic involvement in UC and the occurrence of esophageal complications. Bivariate analyses were conducted using the chi-squared test or Fisher exact test (two-tailed). Results: A higher prevalence of GERD (23.0% vs. 16.5%) and GERD phenotypes, such as non-erosive reflux disease (NERD) (22.3% vs. 16%) and erosive esophagitis (EE) (1.2% vs. 0.6%), was found in UC patients (p < 0.01), including pancolitis, proctitis, proctosigmoiditis, left-sided colitis, and indetermined UC (with undefined colonic involvement). UC patients were more likely to develop GERD (1.421), NERD (1.407), and EE (1.681) (p < 0.01). A higher prevalence of esophageal stricture (16.9 vs. 11.4 per 10,000 patients) and BE without dysplasia (94.5 vs. 39.3 per 10,000 patients) was found in UC (p < 0.05). The odds of developing BE without dysplasia were higher (1.892) in patients with UC (p < 0.01), including ulcerative pancolitis, proctitis, and indeterminate UC (OR of 1.657, 3.328, and 1.996, respectively) (p < 0.05). Conclusions: Our study demonstrates an increased risk of developing GERD and its complications in UC. This highlights the importance of vigilant monitoring and early intervention to minimize associated GERD-related risks in patients with UC.

show abstract

The Promise of Polygenic Risk Scores as a Research Tool to Analyse the Genetics Underlying IBD Phenotypes

Cited by 3 publications

References 11 publications

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

Are We Ready to Reclassify Crohn’s Disease Using Molecular Classification?

A Polygenic Risk Analysis for Identifying Ulcerative Colitis Patients with European Ancestry

Enhanced Risk of Gastroesophageal Reflux Disease and Esophageal Complications in the Ulcerative Colitis Population

Contact Info

Product

Resources

About