Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.

/pdf/biological-insights-from-108-schizophrenia-associated-3rfvth8dm9.pdf

Biological insights from 108 schizophrenia-associated genetic loci

Secret History: Return of the Black Death Channel 4, 7-8pm In 1348 the Black Death swept through London, killing people within days of the appearance of their first symptoms. Exactly how many died, and why, has long been a mystery. This Secret History documentary follows experts as they pick through the evidence and reveal why the plague killed on such a scale. And they ask, what might be coming next?

Medscape

The reference human genome sequence set the stage for studies of genetic variation and its association with human disease, but epigenomic studies lack a similar reference. To address this need, the NIH Roadmap Epigenomics Consortium generated the largest collection so far of human epigenomes for primary cells and tissues. Here we describe the integrative analysis of 111 reference human epigenomes generated as part of the programme, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression. We establish global maps of regulatory elements, define regulatory modules of coordinated activity, and their likely activators and repressors. We show that disease- and trait-associated genetic variants are enriched in tissue-specific epigenomic marks, revealing biologically relevant cell types for diverse human traits, and providing a resource for interpreting the molecular basis of human disease. Our results demonstrate the central role of epigenomic information for understanding gene regulation, cellular differentiation and human disease.

/pdf/integrative-analysis-of-111-reference-human-epigenomes-4bavnjaon6.pdf

Integrative analysis of 111 reference human epigenomes

Understanding the functional consequences of genetic variation, and how it affects complex human disease and quantitative traits, remains a critical challenge for biomedicine. We present an analysi...

The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans

The emerging role of faecal microbiota transplantation

Prospective Evaluation of Early Post-Operative Crohn's Recurrence in the Presence of Optimal Drug Therapy – Is Endoscopic Evaluation Worthwhile?

See article in J. Gastroenterolol. Hepatol. 2011; 26: 1114–1122.

Le plus ca change: why we need better biomarkers to predict outcomes in ulcerative colitis.

The effect of dietary supplementation with glucose on appetite and antropyloroduodenal motility

in clopidogrel users: a nationwide population-based study. Aliment Pharmacol Ther. 2013;38:1119-1128. 5. Lu e A, Lanas A. Protons pump inhibitor treatment and lower gastrointestinal bleeding: balancing risks and benefits. World J Gastroenterol. 2016;22:10477-10481. 6. Washio E, Esaki M, Maehata Y, et al. Proton pump inhibitors increase incidence of nonsteroidal anti-Inflammatory drug-induced small bowel injury: a randomized, placebo-controlled trial. Clin Gastroenterol Hepatol. 2016;14:809–815, e1. 7. Montalto M, Gallo A, Curigliano V, et al. Clinical trial: the effects of a probiotic mixture on non-steroidal anti-inflammatory drug enteropathy a randomized, double-blind, cross-over, placebo-controlled study. Aliment Pharmacol Ther. 2010;32:209-214. 8. Endo H, Higurashi T, Hosono K, et al. Efficacy of Lactobacillus casei treatment on small bowel injury in chronic low-dose aspirin users: a pilot randomized controlled study. J Gastroenterol. 2011;46:894-905. 9. Watanabe T, Sugimori S, Kameda N, et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study. Clin Gastroenterol Hepatol. 2008;6:1279-1282. 10. Taha AS. Misoprostol for small bowel ulcers and obscure bleeding due to aspirin or nonsteroidal anti-inflammatory drugs (MASTERS). https://clinicaltrials.gov/ct2/show/NCT02202967 Accessed April 2, 2017.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/apt.14115

Jane M. Andrews

Papers

The emerging role of faecal microbiota transplantation

Prospective Evaluation of Early Post-Operative Crohn's Recurrence in the Presence of Optimal Drug Therapy – Is Endoscopic Evaluation Worthwhile?

Le plus ca change: why we need better biomarkers to predict outcomes in ulcerative colitis.

The effect of dietary supplementation with glucose on appetite and antropyloroduodenal motility

Editorial: yoga for QoL in ulcerative colitis—any better than other supportive activities?