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Inflammatory bowel disease (IBD) is highly prevalent among the Ashkenazi Jewish population. Here, the authors identify novel IBD-associated variants and genes, validated by transcriptomic and phenome-wide associations.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

Richard Duerr and colleagues present a genome-wide association study of ulcerative colitis. They identify new risk loci on chromosomes 1p36 and 12q15.

While hundreds of loci are linked with inflammatory bowel diseases (IBDs), the functional consequences of the associated variants remain unclear. Here, the authors screened in ulcerative colitis (UC) patients’ genomes for protein-truncating variants near IBD loci, and identify a protein truncating variant in RNF186to be protective against UC.

Quantifying intact proviruses is key to understanding decreases in HIV reservoirs but results can differ depending on the method. To balance sensitivity and specificity of two assays, the authors use mathematical models and measurements of intact and defective proviruses to assess how misclassification can impact estimates of natural and therapeutic reservoir reduction.

Mark Daly and colleagues present results of a combined analysis of data from three recent genome-wide association studies for Crohn's disease, followed by replication in a large independent sample collection. Their results confirm 11 previously reported risk loci and provide genome-wide significant evidence for 21 new loci associated with the disease.

Mark Daly, Manuel Rivas and colleagues used next-generation sequencing to study the coding exons of 56 genes from regions previously associated with Crohn's disease. Follow-up analyses in independent case-control series confirmed association of many newly discovered rare variants with disease risk.

Genome-wide association analyses across individuals of East Asian and European ancestries identify new risk loci for inflammatory bowel diseases. A polygenic risk score derived from the combined datasets shows improved prediction accuracy.

Neuroinflammation is observed in Alzheimer’s disease. Here the authors show that 15 proteins related to inflammation found in CSF can potentially be used as a prognostic biomarker.

Mark Daly, Ramnik Xavier and colleagues report that a 20-kb deletion polymorphism upstream of IRGM is associated with altered IRGM expression and Crohn's disease. They also show that manipulation of IRGM levels in cells modulated the efficiency of autophagic responses to internalized bacteria, suggesting a mechanism by which the deletion variant might influence disease risk.

In this Review, Karimy et al. discuss the mechanisms by which inflammation can contribute to the pathogenesis of acquired hydrocephalus and highlight targets for therapeutic intervention.

Miles Parkes and colleagues report results of a large genome-wide association meta-analysis and replication study for Crohn's disease. They identify 30 new susceptibility loci for this inflammatory bowel disease and implicate several interesting candidate genes in disease pathogenesis.

John Rioux and colleagues report results of a large genome-wide association meta-analysis and follow-up study of ulcerative colitis. They identify 29 new risk loci for this inflammatory disease and show that many risk loci are shared between ulcerative colitis and Crohn's disease.

Mark Seielstad and colleagues report results of a large genome-wide association and replication study of ulcerative colitis. The work identifies several new risk loci for this disease and provides further insight into the shared pathogenesis of ulcerative colitis and Crohn's disease.

Most of the more than 200 known genetic risk loci for inflammatory bowel disease (IBD) reside in regulatory regions. Here, the authors provide eQTL datasets for six circulating immune cell types and ileal, colonic and rectal biopsies to map regulatory modules and identify potential causative genes for IBD.

A meta-analysis of previous genome-wide association studies of Crohn’s disease and ulcerative colitis, the two most common forms of inflammatory bowel disease, with a combined total of more than 75,000 cases and controls, finds that most loci contribute to both phenotypes and other immune-mediated disorders.

John Rioux, Andre Franke, Tom Karlsen and colleagues perform a fine-mapping study of the HLA region in Crohn's disease and ulcerative colitis. They identify a primary role for HLA-DRB1*01:03 in both diseases and find evidence of heterozygous advantage in protection against ulcerative colitis.