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

Su1318 Intestinal Resection in Crohn's Disease Is Associated With Significant and Durable Improvement in Health Related Quality of Life Although to a Lesser Extent in Women and Smokers. Results From the POCER Study

Mo2071 A Placebo Controlled Randomised Treatment Trial for Functional Dyspepsia Including Post-Treatment Drug Withdraw and Placebo Withdraw Effects

Are all symptoms in patients in IBD due to occult inflammation

944 Female Gender and Surgery Lead to Greater Perceived Impact of Inflammatory Bowel Disease (IBD) On Body Image and Sexual Function: A Neglected Issue

Background: This study aimed to explore the course of depression and anxiety in chronic hepatitis C patients. Methods: Data were combined from two studies: (1) Hospital Anxiety and Depression Scale (HADS) scores in 395 con- secutive Australian outpatients from 2006 to 2010 formed the baseline measurement; and (2) Depression Anxiety Stress Scales (DASS) scores in a survey of a sub-sample of these patients in 2011 formed the follow-up measurement. After converting DASS to HADS scores, changes in symptom scores and rates of case-ness (� 8), and predictors of follow-up symptoms were assessed. Results: Follow-up data were available for 61 patients (70.5% male) whose age ranged from 24.5 to 74.6 years (M=45.6). The time to follow-up ranged from 20.7 to 61.9 months (M=43.8). Baseline rates of depres- sion (32.8%) and anxiety (44.3%) increased to 62.3% and 67.2%, respectively. These findings were confirmed, independ- ent of the conversion, by comparing baseline HADS and follow-up DASS scores with British community norms. Baseline anxiety and younger age predicted depression, while baseline anxiety, high school non-completion, and single relationship status predicted anxiety. Conclusion: This study demonstrated a worsening trajectory of depression and anxiety. Further controlled and prospective research in a larger sample is required to confirm these findings.

/pdf/an-aggravated-trajectory-of-depression-and-anxiety-co-morbid-9z7pcierw2.pdf

Jane M. Andrews

Papers

Su1318 Intestinal Resection in Crohn's Disease Is Associated With Significant and Durable Improvement in Health Related Quality of Life Although to a Lesser Extent in Women and Smokers. Results From the POCER Study

Mo2071 A Placebo Controlled Randomised Treatment Trial for Functional Dyspepsia Including Post-Treatment Drug Withdraw and Placebo Withdraw Effects

Are all symptoms in patients in IBD due to occult inflammation

944 Female Gender and Surgery Lead to Greater Perceived Impact of Inflammatory Bowel Disease (IBD) On Body Image and Sexual Function: A Neglected Issue

An Aggravated Trajectory of Depression and Anxiety Co-morbid with Hepatitis C: A Within-groups Study of 61 Australian Outpatients.