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Genetic insights into common pathways and complex relationships among immune-mediated diseases.
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TLDR
It is revealed that several diseases share multiple susceptibility loci, but there are many nuances that help explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.Abstract:
Shared aetiopathogenic factors among immune-mediated diseases have long been suggested by their co-familiality and co-occurrence, and molecular support has been provided by analysis of human leukocyte antigen (HLA) haplotypes and genome-wide association studies. The interrelationships can now be better appreciated following the genotyping of large immune disease sample sets on a shared SNP array: the 'Immunochip'. Here, we systematically analyse loci shared among major immune-mediated diseases. This reveals that several diseases share multiple susceptibility loci, but there are many nuances. The most associated variant at a given locus frequently differs and, even when shared, the same allele often has opposite associations. Interestingly, risk alleles conferring the largest effect sizes are usually disease-specific. These factors help to explain why early evidence of extensive 'sharing' is not always reflected in epidemiological overlap.read more
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Elements of cancer immunity and the cancer–immune set point
Daniel S. Chen,Ira Mellman +1 more
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10 Years of GWAS Discovery: Biology, Function, and Translation
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Journal ArticleDOI
Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.
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Journal ArticleDOI
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TL;DR: A fine-mapping algorithm is developed to identify candidate causal variants for 21 autoimmune diseases from genotyping data, and it is found that most non-coding risk variants, including those that alter gene expression, affect non-canonical sequence determinants not well-explained by current gene regulatory models.
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
TL;DR: A better understanding of how these variables cooperate to affect tumour–host interactions is needed to optimize the implementation of precision immunotherapy.
References
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Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
Lam C. Tsoi,Sarah L. Spain,Jo Knight,Eva Ellinghaus,Philip E. Stuart,Francesca Capon,Jun Ding,Yun Li,Trilokraj Tejasvi,Johann E. Gudjonsson,Hyun Min Kang,Mariet Allen,Ross McManus,Giuseppe Novelli,Lena Samuelsson,J. Schalkwijk,Mona Ståhle,A D Burden,Catherine H. Smith,Michael J. Cork,Xavier Estivill,Anne M. Bowcock,Gerald G. Krueger,Wolfgang Weger,Jane Worthington,Rachid Tazi-Ahnini,Frank O. Nestle,Adrian Hayday,Per Hoffmann,Juliane Winkelmann,Cisca Wijmenga,Cordelia Langford,Sarah Edkins,Ross M. Andrews,H. D. Blackburn,A. Strange,Richard D. Pearson,Damjan Vukcevic,Chris C. A. Spencer,Panagiotis Deloukas,Ulrich Mrowietz,Stefan Schreiber,Stephan Weidinger,Sulev Kõks,Külli Kingo,Tõnu Esko,Andres Metspalu,Henry W. Lim,John J. Voorhees,Michael Weichenthal,H. E. Wichmann,Vinod Chandran,Cheryl F. Rosen,Proton Rahman,Dafna D. Gladman,Christopher E.M. Griffiths,André Reis,Juha Kere,R. P. Nnair,Andre Franke,J. Barker,Gonçalo R. Abecasis,J. T. Eelder,R. Ttrembath,Kristina Callis Duffin,Cynthia Helms,David E. Goldgar,Justin Paschall,Mary J. Malloy,Clive R. Pullinger,John P. Kane,Jennifer M. Gardner,A. Perlmutter,Andrew Miner,Bing Jian Feng,Ravi Hiremagalore,Robert W. Ike,Enno Christophers,Tilo Henseler,Andreas Ruether,Steven J. Schrodi,Sampath Prahalad,Stephen L. Guthery,Judith Fischer,Wilson Liao,Pui-Yan Kwok,Alan Menter,G.M. Lathrop,Carol Wise,Ann B. Begovich,Alexandros Onoufriadis,Michael E. Weale,Anne C. Hofer,Wolfgang Salmhofer,Philip A. Wolf,Kati Kainu,Ulpu Saarialho-Kere,Sari Suomela,P. Badorf,Ulrike Hüffmeier,Werner Kurrat,Wolfgang Küster,Jesús Lascorz,Rotraut Mössner,Funda Schürmeier-Horst,Markward Ständer,Horst Traupe,Judith G.M. Bergboer,Martin den Heijer,P.C.M. van de Kerkhof,Patrick L.J.M. Zeeuwen,L. Barnes,Linda E. Campbell,Caitriona Cusack,C. M. Coleman,Judith Conroy,Sean Ennis,Oliver FitzGerald,Phil Gallagher,Alan D. Irvine,Brian Kirby,Trevor Markham,Whi McLean,Joseph McPartlin,Sarah Rogers,Anthony W. Ryan,Agnieszka Zawirska,Emiliano Giardina,Tiziana Lepre,Carlo Perricone,Gemma Martin-Ezquerra,Ramon M. Pujol,Eva Riveira-Muñoz,Annica Inerot,Åsa Torinsson Naluai,Lotus Mallbris,Katarina Wolk,Joyce Leman,Anne Barton,Richard B. Warren,Helen S. Young,Isis Ricaño-Ponce,Gosia Trynka,Fawnda Pellett,A. Henschel,M. Aurand,Bruce F. Bebo,Christian Gieger,Thomas Illig,Susanne Moebus,K. H. Jöckel,Raimund Erbel,Peter Donnelly,Leena Peltonen,Jenefer M. Blackwell,Elvira Bramon,Matthew A. Brown,Juan P. Casas,Aiden Corvin,N. Craddock,Audrey Duncanson,Janusz Jankowski,Hugh S. Markus,Christopher G. Mathew,Mark I. McCarthy,Colin N. A. Palmer,Robert Plomin,Anna Rautanen,Stephen Sawcer,Nilesh J. Samani,Ananth C. Viswanathan,Nicholas W. Wood,Céline Bellenguez,Colin Freeman,Garrett Hellenthal,Eleni Giannoulatou,Matti Pirinen,Zhan Su,Sarah E. Hunt,R. Gwilliam,Suzannah Bumpstead,Serge Dronov,Matthew W. Gillman,Erin Gray,Naomi Hammond,Alagurevathi Jayakumar,O. T. McCann,Jennifer Liddle,Maritza Pérez,Simon C. Potter,Radhi Ravindrarajah,Michelle Ricketts,Matthew Waller,Paul A. Weston,Sara Widaa,Pamela Whittaker,R. P. Neir,J.N.W.N. Barker,James T. Elder,Richard C. Trembath +199 more
TL;DR: A meta-analysis of genome-wide association studies and independent data sets genotyped on the Immunochip identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals, and identified five independent signals within previously known loci.
Journal ArticleDOI
Identifying Relationships among Genomic Disease Regions: Predicting Genes at Pathogenic SNP Associations and Rare Deletions
Soumya Raychaudhuri,Robert M. Plenge,Robert M. Plenge,Robert M. Plenge,Elizabeth J. Rossin,Elizabeth J. Rossin,Elizabeth J. Rossin,Aylwin Ng,Shaun Purcell,Shaun Purcell,Pamela Sklar,Edward M. Scolnick,Edward M. Scolnick,Ramnik J. Xavier,David Altshuler,Mark J. Daly,Mark J. Daly +16 more
TL;DR: A statistical method that takes a list of disease regions and automatically assesses the degree of relatedness of implicated genes using 250,000 PubMed abstracts, and offers a statistically robust approach to identifying functionally related genes from across multiple disease regions—that likely represent key disease pathways.
Journal ArticleDOI
Genome-wide association analysis identifies new susceptibility loci for Behçet's disease and epistasis between HLA-B*51 and ERAP1
Yohei Kirino,George Bertsias,George Bertsias,Yoshiaki Ishigatsubo,Nobuhisa Mizuki,Ilknur Tugal-Tutkun,Emire Seyahi,Yilmaz Ozyazgan,F Sevgi Sacli,Burak Erer,Hidetoshi Inoko,Zeliha Emrence,Atilla Cakar,Neslihan Abaci,Duran Ustek,Colleen Satorius,Atsuhisa Ueda,Mitsuhiro Takeno,Yoonhee Kim,Geryl Wood,Michael J. Ombrello,Akira Meguro,Ahmet Gül,Elaine F. Remmers,Daniel L. Kastner +24 more
TL;DR: A genome-wide association study of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behçet's disease and 1,278 controls found new associations at CCR1, STAT4 and KLRC4, and found evidence for interaction between HLA-B*51 and ERAP1.
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