High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis.

This is the author accepted manuscript. The final version is available from NPG at http://www.nature.com/ng/journal/v47/n2/full/ng.3176.html#acknowledgmentsGenome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in >32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.We would like to thank the International PSC study group (http://www.ipscsg.org/) for sharing data. We are grateful to B.A. Lie and K. Holm for helpful discussions. J.D.R. holds a Canada Research Chair, and this work was supported by a US National Institute of Diabetes and Digestive and Kidney Diseases grant (NIDDK; R01 DK064869 and U01 DK062432). The laboratory of A.F. is supported by the German Ministry of Education and Research (BMBF) grant program e:Med (sysINFLAME). A.F. receives infrastructure support from the Deutsche Forschungsgemeinschaft (DFG) Cluster of Excellence 'Inflammation at Interfaces' and holds an endowment professorship (Peter Hans Hofschneider Professorship) of the Foundation for Experimental Biomedicine (Zurich, Switzerland). Grant support for T.H.K. and A.F. was received from the European Union Seventh Framework Programme (FP7/2007-2013, grant number 262055, ESGI). M.N.C. is supported by the Intramural Research Program of the US National Institutes of Health (NIH), Frederick National Laboratory, Center for Cancer Research. This project has been funded in whole or in part with federal funds from the Frederick National Laboratory for Cancer Research, under contract HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the US Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US government. J.C.B. was supported by a Wellcome Trust grant (WT098051). D.M. and V.K. are supported by the NIHR Cambridge Biomedical Research Centre. L.P.S. is supported by an NIDDK grant (U01 DK062429-14). J.A.T. is supported by the UK Medical Research Council. D.P.B.M. is supported by the Leona M. and Harry B. Helmsley Charitable Trust, the European Union (305479) and by grants from the NIDDK (U01 DK062413, P01 DK046763-19, U54 DE023789-01), the National Institute of Allergy and Infectious Diseases (NIAID; U01 AI067068) and the Agency for Healthcare Research and Quality (AHRQ; HS021747). R.H.D. holds the Inflammatory Bowel Disease Genetic Research endowed chair at the University of Pittsburgh and was supported by an NIDDK grant (U01 DK062420) and a US National Cancer Institute grant (CA141743). S.L.H. and J.R.O. would like to also acknowledge the support of the US NIH (R01 NS049477 and 1U19 A1067152) and the National Multiple Sclerosis Society (RG 2899-D11). S.L. wishes to acknowledge support from the Australian National Health and Medical Research Council (R.D. Wright Career Development Fellowship, APP1053756)

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Estimation and partitioning of (co)heritability of inflammatory bowel disease from GWAS and immunochip data

As custom arrays are cheaper than generic GWAS arrays, larger sample size is achievable for gene discovery. Custom arrays can tag more variants through denser genotyping of SNPs at associated loci, but at the cost of losing genome-wide coverage. Balancing this trade-off is important for maximizing experimental designs. We quantified both the gain in captured SNP-heritability at known candidate regions and the loss due to imperfect genome-wide coverage for inflammatory bowel disease using immunochip (iChip) and imputed GWAS data on 61 251 and 38 550 samples, respectively. For Crohn's disease (CD), the iChip and GWAS data explained 19 and 26% of variation in liability, respectively, and SNPs in the densely genotyped iChip regions explained 13% of the SNP-heritability for both the iChip and GWAS data. For ulcerative colitis (UC), the iChip and GWAS data explained 15 and 19% of variation in liability, respectively, and the dense iChip regions explained 10 and 9% of the SNP-heritability in the iChip and the GWAS data. From bivariate analyses, estimates of the genetic correlation in risk between CD and UC were 0.75 (SE 0.017) and 0.62 (SE 0.042) for the iChip and GWAS data, respectively. We also quantified the SNP-heritability of genomic regions that did or did not contain the previous 163 GWAS hits for CD and UC, and SNP-heritability of the overlapping loci between the densely genotyped iChip regions and the 163 GWAS hits. For both diseases, over different genomic partitioning, the densely genotyped regions on the iChip tagged at least as much variation in liability as in the corresponding regions in the GWAS data, however a certain amount of tagged SNP-heritability in the GWAS data was lost using the iChip due to the low coverage at unselected regions. These results imply that custom arrays with a GWAS backbone will facilitate more gene discovery, both at associated and novel loci

Silent embolic infarcts on computed tomographybrain scans and risk of ipsilateral hemisphericevents in patients with asymptomatic internalcarotid artery stenosis

Objectives: This study tested the hypothesis that silent embolic infarcts on computed tomography (CT) brain scans can predict ipsilateral neurologic hemispheric events and stroke in patients with asymptomatic internal carotid artery stenosis. Methods: In a prospective multicenter natural history study, 821 patients with asymptomatic carotid stenosis graded with duplex scanning who had CT brain scans were monitored every 6 months for a maximum of 8 years. Duplex scans were reported centrally, and stenosis was expressed as a percentage in relation to the normal distal internal carotid criteria used by the North American Symptomatic Carotid Endarterectomy Trialists. CT brain scans were reported centrally by a neuroradiologist. In 146 patients (17.8%), 8 large cortical, 15 small cortical, 72 discrete subcortical, and 51 basal ganglia ipsilateral infarcts were present; these were considered likely to be embolic and were classified as such. Other infarct types, lacunes (n = 15), watershed (n = 9), and the presence of diffuse white matter changes (n = 95) were not considered to be embolic. Results: During a mean follow-up of 44.6 months (range, 6 months-8 years), 102 ipsilateral hemispheric neurologic events (amaurosis fugax in 16, 38 transient ischemic attacks [TIAs], and 47 strokes) occurred, 138 patients died, and 24 were lost to follow-up. In 462 patients with 60% to 99% stenosis, the cumulative event-free rate at 8 years was 0.81 (2.4% annual event rate) when embolic infarcts were absent and 0.63 (4.6% annual event rate) when present (log-rank P = .032). In 359 patients with <60% stenosis, embolic infarcts were not associated with increased risk (log-rank P = .65). In patients with 60% to 99% stenosis, the cumulative stroke-free rate was 0.92 (1.0% annual stroke rate) when embolic infarcts were absent and 0.71 (3.6% annual stroke rate) when present (log-rank P = .002). In the subgroup of 216 with moderate 60% to 79% stenosis, the cumulative TIA or stroke-free rate in the absence and presence of embolic infarcts was 0.90 (1.3% annual rate) and 0.65 (4.4% annual rate), respectively (log-rank P = .005). Conclusion: The presence of silent embolic infarcts can identify a high-risk group for ipsilateral hemispheric neurologic events and stroke and may prove useful in the management of patients with moderate asymptomatic carotid stenosis

International Social Survey Programme: Health and Health Care - ISSP 2011

Beurteilung des Gesundheitssystems im Land. Persönliche Gesundheit.Gesundheitsversicherung. Themen: Lebenszufriedenheit (Glücklichsein); Vertrauen in dasBildungssystem und das Gesundheitssystem des Landes; Forderung nacheiner Änderung des Gesundheitssystems; Rechtfertigung besserermedizinischer Versorgung und Bildung für Personen mit höheremEinkommen; Beurteilung des Gesundheitssystems des Landes (Skala:Einschätzung der Verbesserung des Gesundheitssystems, Beanspruchung vonGesundheitsleistungen über den notwendigen Bedarf hinweg,Bereitstellung von Basisgesundheitsleistungen durch den Staat,ineffizientes Gesundheitssystem); Bereitschaft zur Zahlung höhererSteuern zur Erhöhung der Gesundheitsversorgung für alle im Land;Einstellung zur öffentlichen Finanzierung von vorbeugendenmedizinischen Checks, Behandlung von HIV/AIDS, Programmen zurVerhinderung von Fettleibigkeit sowie Organtransplantationen;Einstellung zum Zugang zu staatlich geförderter Gesundheitsversorgungfür Menschen mit fremder Staatsbürgerschaft bzw. selbstschädigendemGesundheitsverhalten; geschätzter Anteil von Menschen ohne Zugang zumGesundheitssystem; Ursachen schwerwiegender Gesundheitsprobleme(gesundheitsschädliches Verhalten, Umwelt, Gene, Armut); Einstellung zurBereitstellung einer Herzoperation für Patienten, die rauchen, dieschon alt sind sowie bei solchen mit jungen Kindern; Einstellung zualternativer Medizin (bessere Lösungen für Gesundheitsprobleme alskonventionelle Medizin, verspricht mehr als sie halten kann);allgemeine Beurteilung von Ärzten im Land (Skala: vertrauenswürdig,diskutieren sämtliche Behandlungsoptionen mit ihren Patienten, geringemedizinische Fähigkeiten, kümmern sich mehr um ihr Einkommen als umihre Patienten, Offenheit im Umgang mit Behandlungsfehlern); Häufigkeitvon Problemen in den letzten vier Wochen: in Bezug auf Arbeit oderHaushaltsaktivitäten aufgrund gesundheitlicher Probleme, körperlichstarke Schmerzen, Unglücklichsein und Depressionen, Verlust desSelbstvertrauens und unüberwindliche Probleme; Häufigkeit vonArztbesuchen und von Besuchen bei alternativen Heilpraktikern imletzten Jahr; Krankenhausaufenthalt im letzten Jahr; Gründe für nichterhaltene notwendige medizinische Behandlung (Zahlungsschwierigkeiten,zeitliche Schwierigkeiten oder andere Verpflichtungen, erforderlicheBehandlung ist am Wohnort nicht verfügbar, zu lange Wartelisten);Wahrscheinlichkeit des Zugangs zur bestmöglichen Behandlung im Land beieiner schweren Krankheit und zu freier Arztwahl; Zufriedenheit mit demGesundheitssystem im Land; Zufriedenheit mit dem letzten Arztbesuch,bei alternativen Heilpraktikern und mit dem letztenKrankenhausaufenthalt; Anzahl täglich gerauchter Zigaretten; Häufigkeitdes Konsums von vier oder mehr alkoholischen Getränken pro Tag;Häufigkeit anstrengender körperlicher Aktivitäten und des Konsums vonObst und Gemüse; Selbsteinschätzung der Gesundheit; chronischeKrankheit oder Behinderung; Größe und Gewicht; Art der persönlichenGesundheitsversicherung; Beurteilung des Schutzes der persönlichenGesundheitsversicherung. Optionale Fragen: Gesundheitsversicherung deckt ab: verordneteMedikamente, zahnmedizinische Versorgung und Krankenhausaufenthalte;Notwendigkeit einer Überweisung des Hausarztes vor dem Besuch einesFacharztes; Einschränkung sozialer Aktivitäten wegen gesundheitlicherProbleme. Demographie: Geschlecht; Alter; Geburtsjahr; Jahre der Schulbildung;Schulbildung (länderspezifisch); höchster Bildungsgrad;Erwerbstätigkeit; Wochenarbeitszeit; Beschäftigungsverhältnis;Beschäftigtenzahl; Vorgesetztenfunktion; Anzahl der beaufsichtigtenBeschäftigten; Art der Organisation; Beruf (ISCO-88);Haupterwerbsstatus; Zusammenleben mit einem Partner;Gewerkschaftsmitgliedschaft; Konfession (länderspezifisch);Konfessionsgruppen; Kirchgangshäufigkeit; Selbsteinschätzung auf einerOben-unten-Skala; Wahlbeteiligung bei der letzten Wahl und gewähltePartei (länderspezifisch); Einschätzung der gewählten Parteilinks-rechts; Ethnizität (länderspezifisch); Kinderzahl;Haushaltsgröße; Einkommen des Befragten (länderspezifisch);Haushaltseinkommen (länderspezifisch); Familienstand;Urbanisierungsgrad; Region (länderspezifisch). Für den Ehepartner bzw. Partner wurde erfragt: Erwerbstätigkeit;Wochenarbeitszeit; Beschäftigungsverhältnis; Vorgesetztenfunktion;Beruf (ISCO-88); Haupterwerbsstatus. Zusätzlich verkodet wurde: Interviewdatum; Case substitution flag;Erhebungsmethode; Gewichtungsfaktor