Human genetics in rheumatoid arthritis guides of high-throughput drug screen of the CD40 signaling pathway, Li G, Diogo D, Wu D, Spoonamore J, Dancik V, Franke F, Kurreeman F, Rossin EJ, Duclos G, Hartland C, Zhou X, Li K, Liu J, De Jager PL, Siminovitch KA, Zhernakova A, Raychaudhuri S, Bowes J, Eyre S, Padyukov L, Gregersen PK, Worthington J, Rheumatoid Arthritis Consortium International (RACI), Gupta N, Clemons PA, Stahl E, Tolliday N, Plenge RM. PLoS Genetics. 2013 May, in progress.
We demonstrate how to leverage human genetics for drug discovery. Genetics of risk of RA points to a pathway (CD40-CD40L signaling) and a HTS assay (NF-kB luciferase-reporter in a B cell line), which was used in a pilot small molecule drug screen at the Broad Institute.