title: Statistical colocalization of genetic risk variants for related autoimmune diseases in the context of common controls.
abstract: Determining whether potential causal variants for related diseases are shared can identify overlapping etiologies of multifactorial disorders. Colocalization methods disentangle shared and distinct causal variants. However, existing approaches require independent data sets. Here we extend two colocalization methods to allow for the shared-control design commonly used in comparison of genome-wide association study results across diseases. Our analysis of four autoimmune diseases--type 1 diabetes (T1D), rheumatoid arthritis, celiac disease and multiple sclerosis--identified 90 regions that were associated with at least one disease, 33 (37%) of which were associated with 2 or more disorders. Nevertheless, for 14 of these 33 shared regions, there was evidence that the causal variants differed. We identified new disease associations in 11 regions previously associated with one or more of the other 3 disorders. Four of eight T1D-specific regions contained known type 2 diabetes (T2D) candidate genes (COBL, GLIS3, RNLS and BCAR1), suggesting a shared cellular etiology.
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Mary D
authors.identifier: 0000000260064343
authors.initials: MD
authors.lastname: Fortune
authors.affiliation: 1] JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. [2] Centre for Biostatistics, Institute of Population Health, University of Manchester, Manchester, UK.
authors.forename: Hui
authors.initials: H
authors.lastname: Guo
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Oliver
authors.identifier: 0000000233885760
authors.initials: O
authors.lastname: Burren
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Ellen
authors.initials: E
authors.lastname: Schofield
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.affiliation: University Neurology Unit, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Ban
authors.affiliation: University Neurology Unit, Addenbrooke's Hospital, Cambridge, UK.
authors.forename: Stephen J
authors.identifier: 0000000176850974
authors.initials: SJ
authors.lastname: Sawcer
authors.affiliation: 1] Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. [2] National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.affiliation: 1] Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. [2] National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.affiliation: 1] Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. [2] National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.affiliation: 1] Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK. [2] National Institute for Health Research Manchester Musculoskeletal Biomedical Research Unit, Central Manchester Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
authors.forename: Steve
authors.initials: S
authors.lastname: Eyre
authors.affiliation: JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.affiliation: 1] JDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, National Institute for Health Research Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK. [2] Medical Research Council Biostatistics Unit, Cambridge Institute of Public Health, Cambridge, UK.
authors.forename: Chris
authors.identifier: 0000000197551703
authors.initials: C
authors.lastname: Wallace
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D001499:Bayes Theorem; D016022:Case-Control Studies; D002446:Celiac Disease / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012306:Risk