A disease-associated gene desert directs macrophage inflammation through ETS2

Abstract Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health 1 . This is compounded by the limited efficacy of available treatments 1 and high failure rates during drug development 2 , highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis 3–6 —we identify that the causal gene, ETS2 , is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that…

• MR
  Medical Research Council

  Awards: MR/M00533X/1, MR/X013626/1, MR/V029711/1