from the contributions of multiple rare SNPs. In such cases a screen for a common SNP associated with an underlying biological effect (such as expression or splicing) is not likely to identify a causal site. Our failure to identify any good strong candidate SNPs controlling expression or splicing associated with disease implicated SNPs in conditions other than autoimmune conditions could reflect a difference in the importance of common variants in autoimmune disease versus other diseases. Such a difference in the role of common variants could be an indirect consequence of selection [25] related to infectious disease, which has created predispositions to autoimmune conditions. In short, outside of autoimmunity, it is possible that many of the reported associations are synthetic, due to multiple rare variants, and therefore the reason that no clear expression or splicing effects have been consistently identified at these loci.
