title: FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.
abstract: Naturally occurring variation in gene copy number is increasingly recognized as a heritable source of susceptibility to genetically complex diseases. Here we report strong association between FCGR3B copy number and risk of systemic lupus erythematosus (P = 2.7 x 10(-8)), microscopic polyangiitis (P = 2.9 x 10(-4)) and Wegener's granulomatosis in two independent cohorts from the UK (P = 3 x 10(-3)) and France (P = 1.1 x 10(-4)). We did not observe this association in the organ-specific Graves' disease or Addison's disease. Our findings suggest that low FCGR3B copy number, and in particular complete FCGR3B deficiency, has a key role in the development of systemic autoimmunity.
authors.affiliation: Physiological Genomics and Medicine Group, UK Medical Research Council (MRC) Clinical Sciences Centre, Imperial College, London W12 0NN, UK.
authors.forename: Manuela
authors.initials: M
authors.lastname: Fanciulli
authors.forename: Penny J
authors.initials: PJ
authors.lastname: Norsworthy
authors.forename: Enrico
authors.initials: E
authors.lastname: Petretto
authors.forename: Rong
authors.initials: R
authors.lastname: Dong
authors.forename: Lorraine
authors.initials: L
authors.lastname: Harper
authors.forename: Lavanya
authors.initials: L
authors.lastname: Kamesh
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Heward
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.forename: Adam
authors.initials: A
authors.lastname: de Smith
authors.forename: Alexandra I F
authors.initials: AI
authors.lastname: Blakemore
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Owen
authors.forename: Simon H S
authors.initials: SH
authors.lastname: Pearce
authors.forename: Luis
authors.initials: L
authors.lastname: Teixeira
authors.forename: Loic
authors.initials: L
authors.lastname: Guillevin
authors.forename: Deborah S Cunninghame
authors.initials: DS
authors.lastname: Graham
authors.forename: Charles D
authors.initials: CD
authors.lastname: Pusey
authors.forename: H Terence
authors.initials: HT
authors.lastname: Cook
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Vyse
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
mesh_terms: D015703:Antigens, CD / Q000235:genetics*; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000235:genetics*; D015551:Autoimmunity / Q000235:genetics*; D004198:Disease Susceptibility; D005602:France / Q000453:epidemiology; D058851:GPI-Linked Proteins; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014890:Granulomatosis with Polyangiitis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000235:genetics*; D017452:Receptors, IgG / Q000235:genetics*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D015703:Antigens, CD; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG