Primary biliary cirrhosis (PBC) is a classical autoimmune liver disease for which effective immunomodulatory therapy is lacking. Here we perform meta-analyses of discovery datasets from genome-wide association studies of European subjects (n=2,764 cases and 10,475 controls) followed by validation genotyping in an independent cohort (n=3,716 cases and 4261 controls). We discover and validate six previously unknown risk loci for PBC (Pcombined<5×10−8) and used pathway analysis to identify JAK-STAT/IL12/IL27 signaling and cytokine-cytokine pathways, for which relevant therapies exist.

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The first substantial comparison between rings and rain wi.th which th~ author is acquainted was made by the astronomer, J. C. Kapteyn of Holland, in 188o and r881 on oaks in the Rhine region. P rofessor Kapteyn has recently prepared and published a brief pamphlet on the subject. 2 A similar comparison between the growth of the great sequoia (Sequoia gigantea), and rainfall is shown in figure I in which the curve for rainfall is from Huntington, 3 from data at Fresno, 70 miles away and 5,000 feet lower in elevation. In s.pite of widely different conditions there is evident reseml'eor.s FrG. r. Comparison • of rainfall at Fresno, Calif.ornia, and growth of sequoias. (Rainfall af•ter Huntington.

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