Characterisation of the genetic architecture of immune mediated disease through informed dimension reduction
Characterisation of the genetic architecture of immune mediated disease through informed dimension reduction
Abstract Genome-wide association studies (GWAS) have uncovered pervasive genetic overlap between common clinically related immune-mediated diseases (IMD). To distinguish axes of IMD risk, and extend genetic knowledge of rare IMDs and subtypes, we developed a Bayesian shrinkage approach to perform a disease-focused decomposition of IMD GWAS summary statistics. We derive 13 components which summarise the multidimensional patterns of IMD genetic risk including those related to raised eosinophil count and serum IP-10. Projection of UK Biobank data demonstrated the IMD-specificity and accuracy of our reduced dimension basis in independent datasets. By projecting 22 rare IMD or IMD subtypes onto the basis we were able to identify disease-discriminating components and suggest novel associations. Requiring only summary level data, our approach allows the genetic architectures across any range of clinically-related traits to be characterised in fewer dimensions, facilitating the analysis of studies with modest sample size, where classical GWAS approaches are challenging.
Reales Guillermo、Burren Oliver S、Wong Limy、Lee James C、Lyons Paul A、Smith Kenneth GC、Wallace Chris、Bowes John、Kirk Paul DW、Thomson Wendy、Barton Anne
Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical CampusCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge Biomedical Campus||MRC Biostatistics Unit, University of Cambridge, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical CampusNational Institute of Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust||Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of ManchesterCambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, University of Cambridge||MRC Biostatistics Unit, University of Cambridge, Cambridge Institute of Public Health, Forvie Site, Robinson Way, Cambridge Biomedical Campus||Cancer Research UK Cambridge Centre, Ovarian Cancer Programme, University of Cambridge Li Ka Shing CentreNational Institute of Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust||Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of ManchesterNational Institute of Health Research Manchester Biomedical Research Centre, Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust||Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester
基础医学生物科学研究方法、生物科学研究技术遗传学
Reales Guillermo,Burren Oliver S,Wong Limy,Lee James C,Lyons Paul A,Smith Kenneth GC,Wallace Chris,Bowes John,Kirk Paul DW,Thomson Wendy,Barton Anne.Characterisation of the genetic architecture of immune mediated disease through informed dimension reduction[EB/OL].(2025-03-28)[2025-06-24].https://www.biorxiv.org/content/10.1101/2020.01.14.905869.点此复制
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