Showing papers by "L. Philip Schumm published in 2020"
TL;DR: Overall loneliness levels are equivalent in England and the U.S. after risk factor adjustment, and the fact that the impact of risk factors were similar across countries suggests that evidence of successful interventions in one country could be leveraged to accelerate development of effective interventions in the other.
15 citations
Icahn School of Medicine at Mount Sinai1, Yale University2, Cedars-Sinai Medical Center3, Cincinnati Children's Hospital Medical Center4, Albert Einstein College of Medicine5, Emory University6, Cardiff University7, University of Chicago8, Boston Children's Hospital9, University of Helsinki10, University of Pittsburgh11, Mount Sinai Hospital, Toronto12, Montreal Heart Institute13, Rutgers University14
TL;DR: It is demonstrated that the rare and high impact genetic architecture of AJ adult IBD displays a significant overlap with very early onset IBD (VEOIBD) genetics, and it is shown that a polygenic risk score (PRS) has high power to differentiate AJ IBD cases from controls when using rare andHigh impact variants.
Abstract: Inflammatory bowel disease (IBD) is a group of chronic diseases, affecting different parts of the gastrointestinal tract, that mainly comprises Crohn9s Disease (CD) and Ulcerative Colitis (UC). Most IBD genomic research to date has involved genome-wide association studies (GWAS) of common genetic variants, mostly in Europeans, resulting in the identification of over 200 risk loci. The incidence of IBD in Ashkenazi Jews (AJ) is particularly high compared to other population groups and rare protein-coding variants are significantly enriched in AJ. These variants are expected to have a larger phenotypic effect and are hypothesized to complement the missing heritability that cannot be fully addressed by GWAS in IBD. Therefore, we genetically identified 4,974 AJs IBD cases and controls from whole exome sequencing (WES) data from the NIDDK IBD Genetics Consortium (IBDGC). We selected credible rare variants with high predicted impact, aggregated them into genes, and performed gene burden and pathway enrichment analyses to identify 7 novel plausible IBD-causing genes：NCF1, CES1, ICAM1, INPP5D, ABCB1, IL33 and TLR4. We further perform bulk and single-cell RNA sequencing, demonstrating the likely relatedness of the novel genes to IBD. Importantly, we demonstrate that the rare and high impact genetic architecture of AJ adult IBD displays a significant overlap with very early onset IBD (VEOIBD) genetics. At the variant level, we performed Phenome-wide association studies (PheWAS) in the UK Biobank to replicate risk sites in IBD and reveal shared risk sites with other diseases. Finally, we showed that a polygenic risk score (PRS) has high power to differentiate AJ IBD cases from controls when using rare and high impact variants.
2 citations