Journal ArticleDOI
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
Citations
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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
Peter M. Visscher,Naomi R. Wray,Qian Zhang,Pamela Sklar,Mark I. McCarthy,Matthew A. Brown,Jian Yang +6 more
TL;DR: The remarkable range of discoveriesGWASs has facilitated in population and complex-trait genetics, the biology of diseases, and translation toward new therapeutics are reviewed.
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Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.
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Genetic and Epigenetic Fine-Mapping of Causal Autoimmune Disease Variants
Kyle Kai-How Farh,Alexander Marson,Jiang Zhu,Markus Kleinewietfeld,William J. Housley,Samantha Beik,Noam Shoresh,Holly Whitton,Russell J.H. Ryan,Alexander A. Shishkin,Meital Hatan,Marlene J. Carrasco-Alfonso,Dita Mayer,C. John Luckey,Nikolaos A. Patsopoulos,Philip L. De Jager,Vijay K. Kuchroo,Charles B. Epstein,Mark J. Daly,David A. Hafler,Bradley E. Bernstein +20 more
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
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References
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Estimation of effect size distribution from genome-wide association studies and implications for future discoveries
Ju-Hyun Park,Sholom Wacholder,Mitchell H. Gail,Ulrike Peters,Kevin B. Jacobs,Stephen J. Chanock,Nilanjan Chatterjee +6 more
TL;DR: Using reported GWAS findings for height, Crohn's disease and breast, prostate and colorectal cancers, it is determined that each of these traits is likely to harbor additional loci within the spectrum of low-penetrance common variants.
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Genetic association of the R620W polymorphism of protein tyrosine phosphatase PTPN22 with human SLE.
Chieko Kyogoku,Carl D. Langefeld,Ward A. Ortmann,Annette Lee,Scott A. Selby,Victoria E.H. Carlton,Monica Chang,Paula S. Ramos,Emily C. Baechler,Franak Batliwalla,Jill Novitzke,Adrienne H. Williams,Clarence Gillett,Peter R. Rodine,Robert R. Graham,Kristin G. Ardlie,Patrick M. Gaffney,Kathy L. Moser,Michelle Petri,Ann B. Begovich,Peter K. Gregersen,Timothy W. Behrens +21 more
TL;DR: Genotyped 525 independent North American white individuals with systemic lupus erythematosus and compared the results with data generated from 1,961 white control individuals provide compelling evidence that PTPN22 plays a fundamental role in regulating the immune system and the development of autoimmunity.
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A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region.
Deborah J. Smyth,Jason D. Cooper,Rebecca Bailey,Sarah F. Field,Oliver S. Burren,Luc J. Smink,Cristian Guja,Constantin Ionescu-Tirgoviste,Barry Widmer,David B. Dunger,David A. Savage,Neil Walker,David Clayton,John A. Todd +13 more
TL;DR: Convincing statistical support for a sixth type 1 diabetes (T1D) locus in the innate immunity viral RNA receptor gene region IFIH1 on chromosome 2q24 is reported.
Journal ArticleDOI
Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci.
Adrian Cortes,Johanna Hadler,J.P. Pointon,Philip Robinson,Tugce Karaderi,Paul Leo,Katie Cremin,Karena Pryce,Jessica Harris,Sang-Gug Lee,Kyung Bin Joo,Shim S-C.,Michael H. Weisman,Minghong Ward,Xiaodong Zhou,Garchon H-J.,Gilles Chiocchia,Johannes C. Nossent,Benedicte A. Lie,Øystein Førre,J. Tuomilehto,J. Tuomilehto,J. Tuomilehto,K. Laiho,Lei Jiang,Yu Liu,Xin Wu,Linda A. Bradbury,Dirk Elewaut,Ruben Burgos-Vargas,Simon Stebbings,Louise Appleton,Claire Farrah,J. Lau,Tony J. Kenna,Nigil Haroon,Manuel A. R. Ferreira,Jian Yang,J Mulero,José Luis Fernández-Sueiro,Miguel A. Gonzalez-Gay,Carlos López-Larrea,Panagiotis Deloukas,Peter Donnelly,Paul Bowness,Karl Gafney,Hill Gaston,Dafna D. Gladman,Dafna D. Gladman,Proton Rahman,Walter P. Maksymowych,Huji Xu,Crusius Jba.,I E van der Horst-Bruinsma,Chou C-T.,R. Valle-Oñate,Consuelo Romero-Sánchez,Inger Myrnes Hansen,Fernando Pimentel-Santos,Robert D. Inman,Vibeke Videm,Javier Martín,Maxime Breban,Maxime Breban,J. D. Reveille,David M. Evans,Kim T-H.,B P Wordsworth,Matthew A. Brown +68 more
TL;DR: In this paper, the authors used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls.
Journal ArticleDOI
High-density genetic mapping identifies new susceptibility loci for rheumatoid arthritis
Steve Eyre,John Bowes,John Bowes,Dorothée Diogo,Dorothée Diogo,Annette Lee,Anne Barton,Anne Barton,Paul Martin,Paul Martin,Alexandra Zhernakova,Alexandra Zhernakova,Eli A. Stahl,Eli A. Stahl,Sebastien Viatte,Sebastien Viatte,Kate McAllister,Kate McAllister,Christopher I. Amos,Leonid Padyukov,René E. M. Toes,Tom W J Huizinga,Cisca Wijmenga,Gosia Trynka,Lude Franke,Harm-Jan Westra,Lars Alfredsson,Xinli Hu,Cynthia Sandor,Cynthia Sandor,Paul I.W. de Bakker,Sonia Davila,Chiea Chuen Khor,Khai Koon Heng,Robert Andrews,Sarah Edkins,Sarah E. Hunt,Cordelia Langford,Deborah P M Symmons,Deborah P M Symmons,Genomics Study Syndicate,Patrick Concannon,Suna Onengut-Gumuscu,Stephen S. Rich,Panos Deloukas,Miguel A. Gonzalez-Gay,Luis Rodriguez-Rodriguez,Lisbeth Ärlsetig,Javier Martin,Solbritt Rantapää-Dahlqvist,Robert M. Plenge,Robert M. Plenge,Soumya Raychaudhuri,Lars Klareskog,Peter K. Gregersen,Jane Worthington,Jane Worthington +56 more
TL;DR: This study illustrates the advantages of dense SNP mapping analysis to inform subsequent functional investigations and refined the peak of association to a single gene for 19 loci, identified secondary independent effects at 6 loci and identified association to low-frequency variants at 4 loci.
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