Human genetics offers an emerging picture of common pathways and mechanisms in autoimmunity

In genetic studies of autoimmune and inflammatory diseases, one clear finding that has emerged from genome-wide association studies is that a substantial fraction of variation modifying risk in one disease also contributes mediate risk to multiple, additional autoimmune and inflammatory diseases. The unexpected magnitude of this overlap presents the unique opportunity to dissect the pathogenic mechanisms underlying multiple disease states in the expectation that this may lead to both more sensitive diagnostics and novel therapies. Here, we review the current evidence for this shared genetic architecture and, based on these data, outline models for shared pathways, the underlying hypotheses for them, how these models can be tested and validated.