title: Imputation of KIR Types from SNP Variation Data.
abstract: Large population studies of immune system genes are essential for characterizing their role in diseases, including autoimmune conditions. Of key interest are a group of genes encoding the killer cell immunoglobulin-like receptors (KIRs), which have known and hypothesized roles in autoimmune diseases, resistance to viruses, reproductive conditions, and cancer. These genes are highly polymorphic, which makes typing expensive and time consuming. Consequently, despite their importance, KIRs have been little studied in large cohorts. Statistical imputation methods developed for other complex loci (e.g., human leukocyte antigen [HLA]) on the basis of SNP data provide an inexpensive high-throughput alternative to direct laboratory typing of these loci and have enabled important findings and insights for many diseases. We present KIR∗IMP, a method for imputation of KIR copy number. We show that KIR∗IMP is highly accurate and thus allows the study of KIRs in large cohorts and enables detailed investigation of the role of KIRs in human disease.
authors.affiliation: Statistical Genetics, Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Damjan
authors.initials: D
authors.lastname: Vukcevic
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: James A
authors.initials: JA
authors.lastname: Traherne
authors.affiliation: Research Institute of Internal Medicine, Department of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital Rikshospitalet, Postboks 4950, Nydalen, 0424 Oslo, Norway; Norwegian PSC Research Center, Division of Cancer, Surgery, and Transplantation, Oslo University Hospital, Postboks 4950, Nydalen, 0424 Oslo, Norway.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Næss
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel, Schittenhelmstraße 12, 24105 Kiel, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Ellinghaus
authors.affiliation: Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 27 Rue Juliette Dodu, 75010 Paris, France; RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kamatani
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Alexander
authors.initials: A
authors.lastname: Dilthey
authors.affiliation: McGill University and Génome Québec Innovation Centre, Montreal, 740 Dr. Penfield Avenue, Room 7104, Montreal, QC H3A 0G1, Canada; Fondation Jean Dausset, Centre d'Etude du Polymorphisme Humain, 27 Rue Juliette Dodu, 75010 Paris, France.
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.affiliation: Research Institute of Internal Medicine, Department of Cancer Medicine, Surgery, and Transplantation, Oslo University Hospital Rikshospitalet, Postboks 4950, Nydalen, 0424 Oslo, Norway; K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Postboks 1171, Blindern, 0318 Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts University of Kiel, Schittenhelmstraße 12, 24105 Kiel, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.affiliation: National Heart and Lung Institute, Imperial College London, Royal Brompton Campus, Dovehouse Street, London SW3 6LY, UK.
authors.forename: Miriam
authors.initials: M
authors.lastname: Moffatt
authors.affiliation: National Heart and Lung Institute, Imperial College London, Royal Brompton Campus, Dovehouse Street, London SW3 6LY, UK.
authors.forename: William
authors.initials: W
authors.lastname: Cookson
authors.affiliation: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK; Division of Immunology, Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK.
authors.forename: John
authors.initials: J
authors.lastname: Trowsdale
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 0QQ, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Sawcer
authors.affiliation: Statistical Genetics, Murdoch Childrens Research Institute, Parkville, VIC 3052, Australia; School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia. Electronic address: stephen.leslie@mcri.edu.au.
authors.forename: Stephen
authors.initials: S
authors.lastname: Leslie
mesh_terms: D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D003876:Dermatitis, Atopic / Q000235:genetics*; D005060:Europe; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054340:Receptors, KIR / Q000145:classification* / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D054340:Receptors, KIR