Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex(MHC) tag SNPsfrom 1,000 independent cases of ankylosing spondylitis(AS), autoimmune thyroiddisease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical powerresulting from the expansion of the control reference groupto include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulationand suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.