Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10 ? ? ). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.

Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

John Calvin's Impact on Church and Society, 1509-2009. Essays for the 500th birthday of Calvin

A tribute to the monumental influence of John Calvin in the 500 years since his birth. / What legacies, still enduring today, have John Calvin and Calvinism given to the church and society in Europe and North America? An international group of scholars tackles that question in this volume honoring Calvin's 500th birthday. These chapters together provide a comprehensive and accessible introduction to Calvin's life and thought, the history of the Reformation in Switzerland and worldwide, and his continuing relevance for ecclesial, social, and political questions today. / Contributors: Philip Benedict, James D. Bratt, Emidio Campi, Wulfert de Greef, Christopher Elwood, Eva-Maria Faber, Eric Fuchs, Ulrich H. J. Krtner, Christian Link, Christian Moser, Andrew Pettegree, Christoph Strohm, Mario Turchetti./ The essays in this book fit beautifully together to provide a solid, complete work that gives precise insight into the many different facets of Calvin and Calvinism. The high-level research found here clearly shows the great impact that Calvin has had on both church and society. It is a great pleasure to see Calvin here anew. Eberhard Busch / University of Gttingen / That John Calvin made a deep and lasting impact on many aspects of history is common knowledge but the character of the man and the nature of his influence are perhaps as controversial as any that can be named. It is thus a challenge to examine even a fraction of the many ways that Calvins life and thought have contributed to the shaping of later ages in both church and society. This volume offers essays on key points from an appropriately international group of authors appreciative but critical, drawing on a rich range of recent scholarship, presented in a pleasing and accessible form. It is a fine place for the new reader of Calvin to get a glimpse of his impact, while offering a fresh summary of some significant issues for more advanced students of the Reformer. Elsie Anne McKee / Princeton Theological Seminary / Hirzel and Sallmann have succeeded in gathering essays by an illustrious circle of experts both historians and theologians on important areas of Calvins thought and impact. Ranging from an insignificant city at the edge of the Swiss Confederation in the 1530s to the Accra Confession of 2004, these essays will serve to correct popular misconceptions. A fine introduction for a broader readership that wants more than mere armchair theology. Peter Opitz / University of Zurich