Unravelling the genetic architecture of inflammatory bowel disease multiplex families with rare and common variant polygenic risk scores.

Background And Aims: Inflammatory bowel disease (IBD) often affects multiple relatives, pointing towards shared genetic and/or environmental factors. This study evaluates the importance of known IBD risk variants, and of genetic determinants of smoking in such multiplex families.

Methods: We studied 65 IBD multiplex families, comprising 146 Crohn's disease [CD], 33 ulcerative colitis [UC], and 111 unaffected relatives.

Results of the 9th Scientific Workshop of the European Crohn's and Colitis Organisation (ECCO): Artificial Intelligence in Endoscopy, Radiology and Histology in IBD Diagnostics.

In this review, a comprehensive overview of the current state of artificial intelligence (AI) research in Inflammatory Bowel Disease (IBD) diagnostics in the domains of endoscopy, radiology and histology is presented. Moreover, key considerations for development of AI algorithms in medical image analysis are discussed. AI presents a potential breakthrough in real-time, objective and rapid endoscopic assessment, with implications for predicting disease progression.

Results of the 9th Scientific Workshop of the European Crohn's and Colitis Organisation (ECCO): Artificial Intelligence in medical management and precision medicine.

Background And Aims: Artificial intelligence (AI) is increasingly being applied in various fields of medicine, including Inflammatory Bowel Diseases (IBD). This systematic review, conducted as part of the ECCO 9th Scientific Workshop on AI in IBD, explores AI applications in multiomic precision medicine, large language models (LLMs) for textual tasks and utilisation of wearable and remote care technologies.

Methods: A comprehensive systematic analysis of the literature was undertaken, emphasising three topics: multiomic predictive models in IBD; natural language processing (NLP) and LLMs for clinical practice, research and patient communication; and the role of remote monitoring and wearable devices.

Results of the 9th Scientific Workshop of the European Crohn's and Colitis Organisation (ECCO): Artificial Intelligence in IBD: Regulatory and Methodological Considerations.

With the rapid growth of artificial intelligence (AI) applications in the field of inflammatory bowel disease (IBD), an increasing number of regulatory and methodological considerations have become apparent. Currently, there remains much uncertainty and limited experience in the field of IBD regarding some of the regulatory and methodological pitfalls to be considered when developing and deploying AI applications for positive clinical and health system impact. Accordingly, an expert panel was convened by the European Crohn's and Colitis Organisation (ECCO) to review the published literature and provide an overview of key regulatory aspects for the application of AI in IBD.

Results of the Ninth Scientific Workshop of the European Crohn's and Colitis Organisation (ECCO): Artificial intelligence in IBD surgery: opportunities and limitations.

In this narrative review we present the current status of developments in artificial intelligence in the filed of IBD surgery. We lay down the foundations for how IBD surgery may utilise the potential opportunities in utilizing the rapid advances in AI technology as it used in other surgical disciplines. The main areas of potential utility are in the areas of surgical training, risk prediction in the pre, intra and post operative period in IBD patients undergoing surgery and in IBD surgical research.

IBD-linked Genetic Variance in Intestinal Transplantation: A Multicenter Cohort Analysis.

Background: In solid organ transplantation, the intestine remains the most challenging. Previous studies have linked NOD2 genetic variation to intestinal transplantation (ITx) outcomes. Since then, a larger set of inflammatory bowel disease-associated genetic variants (IBDGVs) has been identified.

Genotype imputation from low-coverage data for medical and population genetic analyses.

Genotype imputation from low-pass sequencing data presents unique opportunities for genomic analyses but comes with specific challenges. In this study, we explore the impact of quality filters on genetic ancestry and Polygenic Score (PGS) estimation after imputing 32,769 low-pass genome-wide sequences (LPS) from noninvasive prenatal screening (NIPS) with an average autosomal sequence depth of ∼0.15×.

Multi-cohort cross-omics analysis reveals disease mechanisms and therapeutic targets in HTLV-1-associated myelopathy, a neglected retroviral neuroinflammatory disorder.

HTLV-1 is an enigmatic retrovirus triggering a debilitating neuroinflammatory disease, HTLV-1-associated myelopathy (HAM), with unknown pathogenesis. Both HTLV-1 infection and HAM predominantly affect women and non-white neglected populations. HAM is lacking disease-modifying treatment, as current treatment is mostly symptomatic and inspired by either HIV-1 or multiple sclerosis therapeutic strategies.

Genomic prediction with kinship-based multiple kernel learning produces hypothesis on the underlying inheritance mechanisms of phenotypic traits.

Background: Genomic prediction encompasses the techniques used in agricultural technology to predict the genetic merit of individuals towards valuable phenotypic traits. It is related to Genome Interpretation in humans, which models the individual risk of developing disease traits. Genomic prediction is dominated by linear mixed models, such as the Genomic Best Linear Unbiased Prediction (GBLUP), which computes kinship matrices from SNP array data, while Genome Interpretation applications to clinical genetics rely mainly on Polygenic Risk Scores.

MIP4IBD: An Easy and Rapid Genotyping-by-Sequencing Assay for the Inflammatory Bowel Diseases Risk Loci.

Background: Inflammatory bowel diseases (IBD) are polygenic, with many genetic variants contributing to disease risk. Knowing the genotype of specific variants or calculating a combined genetic risk score benefits translational and functional research. To address this, we developed MIP4IBD, a flexible and cost-effective genotyping-by-sequencing assay using molecular inversion probes (MIPs).

Plasma pTau181 and pTau217 predict asymptomatic amyloid accumulation equally well as amyloid PET.

The dynamic phase of preclinical Alzheimer's disease, as characterized by accumulating cortical amyloid-β, is a window of opportunity for amyloid-β-lowering therapies to have greater efficacy. Biomarkers that accurately predict amyloid-β accumulation may be of critical importance for participant inclusion in secondary prevention trials and thus enhance development of early Alzheimer's disease therapies. We compared the abilities of baseline plasma pTau181, pTau217 and amyloid-β PET load to predict future amyloid-β accumulation in asymptomatic elderly.

Longitudinal APOE4- and amyloid-dependent changes in the blood transcriptome in cognitively intact older adults.

Background: Gene expression is dysregulated in Alzheimer's disease (AD) patients, both in peripheral blood and post mortem brain. We investigated peripheral whole-blood gene (co)expression to determine molecular changes prior to symptom onset.

Methods: RNA was extracted and sequenced for 65 cognitively healthy F-PACK participants (65 (56-80) years, 34 APOE4 non-carriers, 31 APOE4 carriers), at baseline and follow-up (interval: 5.

Genomic analyses of hair from Ludwig van Beethoven.

Ludwig van Beethoven (1770-1827) remains among the most influential and popular classical music composers. Health problems significantly impacted his career as a composer and pianist, including progressive hearing loss, recurring gastrointestinal complaints, and liver disease. In 1802, Beethoven requested that following his death, his disease be described and made public.

The genetics of non-monogenic IBD.

Inflammatory bowel disease (IBD), with Crohn's disease and ulcerative colitis as main subtypes, is a prototypical multifactorial disease with both genetic and environmental factors involved. Genetically, IBD covers a wide spectrum from monogenic to polygenic forms. In polygenic disease, many genetic variants each contribute a small amount to disease risk.

Association of Alzheimer's disease polygenic risk scores with amyloid accumulation in cognitively intact older adults.

Background: Early detection of individuals at risk for Alzheimer's disease (AD) is highly important. Amyloid accumulation is an early pathological AD event, but the genetic association with known AD risk variants beyond the APOE4 effect is largely unknown. We investigated the association between different AD polygenic risk scores (PRS) and amyloid accumulation in the Flemish Prevent AD Cohort KU Leuven (F-PACK).

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility.

Genome-wide association studies (GWASs) have identified hundreds of loci associated with Crohn's disease (CD). However, as with all complex diseases, robust identification of the genes dysregulated by noncoding variants typically driving GWAS discoveries has been challenging. Here, to complement GWASs and better define actionable biological targets, we analyzed sequence data from more than 30,000 patients with CD and 80,000 population controls.

Assessing aCCess to Investigations in Inflammatory Bowel Disease (ACCID): results from an international survey.

Background: Multiple investigations are available to aid the diagnosis and monitoring of disease activity in inflammatory bowel disease (IBD). Fecal calprotectin (FC) is an established surrogate for intestinal inflammatory activity. Therapeutic drug monitoring (TDM) including thiopurine metabolites, anti-tumor necrosis factor (TNF) levels and antidrug antibody measurements are a step toward personalized medicine in IBD, but face access barriers.

Oncostatin M Is a Biomarker of Diagnosis, Worse Disease Prognosis, and Therapeutic Nonresponse in Inflammatory Bowel Disease.

Background: Oncostatin M (OSM) has been implicated in the pathogenesis of inflammatory bowel disease (IBD) and as a marker for nonresponsiveness to anti-tumor necrosis factor (TNF) therapy. We further unraveled the potential of OSM and related receptors as markers of diagnosis, prognosis, and therapy response in IBD.

Methods: We collected inflamed mucosal biopsies and serum from patients with Crohn disease (CD) and with ulcerative colitis: (1) newly diagnosed patients who were treatment-naïve, (2) patients initiating anti-TNF or (3) vedolizumab therapy, (4) postoperative patients with CD, and (5) multiple-affected families with IBD including unaffected first-degree relatives (FDRs).

An interpretable low-complexity machine learning framework for robust exome-based - diagnosis of Crohn's disease patients.

Whole exome sequencing (WES) data are allowing researchers to pinpoint the causes of many Mendelian disorders. In time, sequencing data will be crucial to solve the puzzle, which aims at uncovering the genotype-to-phenotype relationship, but for the moment many conceptual and technical problems need to be addressed. In particular, very few attempts at the in-silico diagnosis of oligo-to-polygenic disorders have been made so far, due to the complexity of the challenge, the relative scarcity of the data and issues such as and data heterogeneity, which are confounder factors for machine learning (ML) methods.

Prostaglandin E receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation.

Objective: Dysfunctional resolution of intestinal inflammation and altered mucosal healing are essential features in the pathogenesis of inflammatory bowel disease (IBD). Intestinal macrophages are vital in the process of inflammation resolution, but the mechanisms underlying their mucosal healing capacity remain elusive.

Design: We investigated the role of the prostaglandin E (PGE) receptor PTGER4 on the differentiation of intestinal macrophages in patients with IBD and mouse models of intestinal inflammation.