FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.
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.
Fanciulli
Manuela
M
Physiological Genomics and Medicine Group, UK Medical Research Council (MRC) Clinical Sciences Centre, Imperial College, London W12 0NN, UK.
Norsworthy
Penny J
PJ
Petretto
Enrico
E
Dong
Rong
R
Harper
Lorraine
L
Kamesh
Lavanya
L
Heward
Joanne M
JM
Gough
Stephen C L
SC
de Smith
Adam
A
Blakemore
Alexandra I F
AI
Froguel
Philippe
P
Owen
Catherine J
CJ
Pearce
Simon H S
SH
Teixeira
Luis
L
Guillevin
Loic
L
Graham
Deborah S Cunninghame
DS
Pusey
Charles D
CD
Cook
H Terence
HT
Vyse
Timothy J
TJ
Aitman
Timothy J
TJ
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
D015703:Antigens, CD; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D017452:Receptors, IgG