ArticleGastroenterology2021
Common and Rare Variant Prediction and Penetrance of IBD in a Large, Multi-ethnic, Health System-based Biobank Cohort.
Article in Gastroenterology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 88 citations in OpenAlex.
- Genome Wide Association Study (GWAS) Identifies Novel Genetic Loci for Second-Generation Antipsychotics (SGA)-Induced Metabolic Syndrome (MetS).Clinical and translational science · 2025Pooled it
- Causal relationship between eosinophilic esophagitis and inflammatory bowel disease: a bidirectional two-sample Mendelian randomization study.Frontiers in immunology · 2024Pooled it
- Polygenic Risk Scores Show Distinct Genetic Architectures of IBD-Associated Comorbidities.Digestive diseases and sciences · 2026Article
- Shaping the research agenda of pediatric gastroenterology, hepatology, and nutrition: The proposal from a SIGENP expert groups.JPGN reports · 2026Review
- Convergent coexpression reveals shared biological mechanisms underlying common and rare variant risk in six neuropsychiatric disorders.Molecular psychiatry · 2026Article
- Gut mucosal barrier: the frontline of bidirectional regulation of the gut-X axis.Medical review (2021) · 2026Review
- IBD Care Across Diverse Patient Populations: Changing the Narrative.Digestive diseases and sciences · 2026Review
- Macrophage MERTK restrains GRAMD1A-driven mitochondrial oxysterol trafficking to limit colitis.Redox biology · 2026Article
- Genomic Insights Into Inflammatory Bowel Disease in United States Hispanic Participants: An Ancestry-Focused Study.Gastroenterology · 2026Article
- Common and rare genetic variants show network convergence for a majority of human traits.EMBO reports · 2026Article
- Polygenic risk scores for Crohn's disease risk prediction in a Chinese population: insights from multi-ethnic genome-wide association studies.European journal of medical research · 2026Article
- Gene, genetics and genetic medicines in gastroenterology: Current status and its future.World journal of gastroenterology · 2026Review
- Branched actin networks mediate macrophage-dependent host-microbiota homeostasis.Science (New York, N.Y.) · 2025Article
- Intestinal barrier in chronic gut and liver diseases: Pathogenesis and therapeutic targets.Acta pharmaceutica Sinica. B · 2025Review
- IBD Prediction Is Possible, but How Far Are We from Implementing It?Inflammatory bowel diseases · 2025Review
- Towards IBD Prediction and Prevention: The Contribution of Genetics and Genomics.Inflammatory bowel diseases · 2025Review
- Assessment of PredictSURE IBD Assay in a Multinational Cohort of Patients With Inflammatory Bowel Disease.United European gastroenterology journal · 2025Article
- Inflammatory bowel disease in paediatrics: Navigating the old challenges and emerging frontiers.World journal of gastroenterology · 2025Review
- Review
- Machine learning-based penetrance of genetic variants.Science (New York, N.Y.) · 2025Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
23 authors at 10 institutions in 4 countries.
Funding
Abstract
BACKGROUND AND
aimsPolygenic risk scores (PRS) may soon be used to predict inflammatory bowel disease (IBD) risk in prevention efforts. We leveraged exome-sequence and single nucleotide polymorphism (SNP) array data from 29,358 individuals in the multiethnic, randomly ascertained health system-based BioMe biobank to define effects of common and rare IBD variants on disease prediction and pathophysiology.
methodsPRS were calculated from European, African American, and Ashkenazi Jewish (AJ) reference case-control studies, and a meta-GWAS run using all three association datasets. PRS were then combined using regression to assess which combination of scores best predicted IBD status in European, AJ, Hispanic, and African American cohorts in BioMe. Additionally, rare variants were assessed in genes associated with very early-onset IBD (VEO-IBD), by estimating genetic penetrance in each BioMe population.
resultsCombining risk scores based on association data from distinct ancestral populations improved IBD prediction for every population in BioMe and significantly improved prediction among European ancestry UK Biobank individuals. Lower predictive power for non-Europeans was observed, reflecting in part substantially lower African IBD case-control reference sizes. We replicated associations for two VEO-IBD genes, ADAM17 and LRBA, with high dominant model penetrance in BioMe. Autosomal recessive LRBA risk alleles are associated with severe, early-onset autoimmunity; we show that heterozygous carriage of an African-predominant LRBA protein-altering allele is associated with significantly decreased LRBA and CTLA-4 expression with T-cell activation.
conclusionsGreater genetic diversity in African populations improves prediction across populations, and generalizes some VEO-IBD genes. Increasing African American IBD case-collections should be prioritized to reduce health disparities and enhance pathophysiological insight.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.