FCGR3B copy number variation is associated with susceptibility to systemic, but not organ-specific, autoimmunity.
Fanciulli M., Norsworthy PJ., Petretto E., Dong R., Harper L., Kamesh L., Heward JM., Gough SC., de Smith A., Blakemore AI., Froguel P., Owen CJ., Pearce SH., Teixeira L., Guillevin L., Graham DS., Pusey CD., Cook HT., Vyse TJ., Aitman TJ.
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.