Journal ArticleDOI
Genetic insights into common pathways and complex relationships among immune-mediated diseases.
Reads0
Chats0
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
More filters
Journal ArticleDOI
Fecal transplants in spondyloarthritis and uveitis: ready for a clinical trial?
TL;DR: This review discusses the available evidence that SpA is a microbiome-driven disease and indicates how SpA-associated uveitis could be tied to gut dysbiosis, and discusses different treatment paradigms targeting the intestinal microbiome for SpA.
Journal ArticleDOI
Major histocompatibility complex harbors widespread genotypic variability of non-additive risk of rheumatoid arthritis including epistasis.
Wenhua Wei,John Bowes,Darren Plant,Sebastien Viatte,Annie Yarwood,Jonathan Massey,Jane Worthington,Stephen Eyre +7 more
TL;DR: In this paper, a two-stage approach was proposed to make vGWAS applicable to diseases: first, using a mixed model approach to partition dichotomous phenotypes into additive risk and non-additive environmental residuals on the liability scale and secondly using the Levene's (Brown-Forsythe) test to assess equality of the residual variances across genotype groups per marker.
Journal ArticleDOI
Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations.
Sigurgeir Olafsson,Pernilla Stridh,Steffan D. Bos,Steffan D. Bos,Andres Ingason,Jack Euesden,Jack Euesden,Jack Euesden,Patrick Sulem,Gudmar Thorleifsson,Omar Gustafsson,Ari Johannesson,Arni Jon Geirsson,Arni V Thorsson,Bardur Sigurgeirsson,Bjorn R. Ludviksson,Bjorn R. Ludviksson,Elias Olafsson,Elias Olafsson,Helga Kristjansdottir,Jon G. Jonasson,Jon G. Jonasson,Jon Hjaltalin Olafsson,Kjartan B. Orvar,Rafn Benediktsson,Ragnar Bjarnason,Ragnar Bjarnason,Sjofn Kristjansdottir,Thorarinn Gislason,Thorarinn Gislason,Trausti Valdimarsson,Evgenia Mikaelsdottir,Snaevar Sigurdsson,Stefan Jonsson,Thorunn Rafnar,Dag Aarsland,Dag Aarsland,Srdjan Djurovic,Tormod Fladby,Gun Peggy Knudsen,Elisabeth Gulowsen Celius,Elisabeth Gulowsen Celius,Kjell-Morten Myhr,Kjell-Morten Myhr,Gerdur Grondal,Kristjan Steinsson,Helgi Valdimarsson,Helgi Valdimarsson,Sigurdur Bjornsson,Unnur S. Bjornsdottir,Einar S. Bjornsson,Einar S. Bjornsson,Björn Nilsson,Ole A. Andreassen,Lars Alfredsson,Lars Alfredsson,Jan Hillert,Ingrid Kockum,Gisli Masson,Unnur Thorsteinsdottir,Unnur Thorsteinsdottir,Daniel F. Gudbjartsson,Daniel F. Gudbjartsson,Hreinn Stefansson,Haukur Hjaltason,Haukur Hjaltason,Hanne F. Harbo,Hanne F. Harbo,Tomas Olsson,I. Jonsdottir,I. Jonsdottir,I. Jonsdottir,Kari Stefansson,Kari Stefansson +73 more
TL;DR: The researchers compared the genetic overlap between various autoimmune diseases in the Icelandic cohort, and documented a close relationship between MS and primary biliary cirrhosis (PBC), and uncovered seven new genetic risk variants linked to MS.
Journal ArticleDOI
A novel approach to genome-wide association analysis identifies genetic associations with primary biliary cholangitis and primary sclerosing cholangitis in Polish patients.
Agnieszka Paziewska,Andrzej Habior,Agnieszka Rogowska,Włodzimierz Zych,Krzysztof Goryca,Jakub Karczmarski,Michalina Dabrowska,Filip Ambrozkiewicz,Bożena Walewska-Zielecka,Marek Krawczyk,Halina Cichoż-Lach,Piotr Milkiewicz,Agnieszka Kowalik,Krzysztof Mucha,Joanna Raczyńska,Joanna Musialik,Grzegorz Boryczka,Michał Wasilewicz,Irena Ciecko-Michalska,Małgorzata Ferenc,Maria Janiak,Alina Kanikowska,Rafał Stankiewicz,Marek Hartleb,Tomasz Mach,Marian Grzymisławski,Joanna Raszeja-Wyszomirska,Ewa Wunsch,Tomasz Bobiński,Michal Mikula,Jerzy Ostrowski +30 more
TL;DR: The authors' cost-effective GWAS approach followed by individual genotyping confirmed several previously identified associations and discovered new susceptibility loci associated with PBC and/or PSC in Polish patients.
Journal ArticleDOI
Therapeutic and Diagnostic Implications of T Cell Scarring in Celiac Disease and Beyond
TL;DR: In this paper, the authors discuss approaches how such T-cells may be targeted for better treatment and diagnosis via their antigen specificity or via their expression of characteristic phenotypic markers.
References
More filters
Journal ArticleDOI
An integrated encyclopedia of DNA elements in the human genome
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
Paul Burton,David Clayton,Lon R. Cardon,Nicholas John Craddock,Panos Deloukas,Audrey Duncanson,Dominic P. Kwiatkowski,Mark I. McCarthy,Willem H. Ouwehand,Nilesh J. Samani,John A. Todd,Peter Donnelly,Jeffrey C. Barrett,Dan Davison,Doug Easton,David M. Evans,H. T. Leung,Jonathan Marchini,Andrew P. Morris,Chris C. A. Spencer,Martin D. Tobin,Antony P. Attwood,James P. Boorman,Barbara Cant,Ursula Everson,Judith M. Hussey,Jennifer Jolley,Alexandra S. Knight,Kerstin Koch,Elizabeth Meech,Sarah Nutland,Christopher Prowse,Helen Stevens,Niall C. Taylor,Graham R. Walters,Neil Walker,Nicholas A. Watkins,Thilo Winzer,Richard Jones,Wendy L. McArdle,Susan M. Ring,David P. Strachan,Marcus Pembrey,Gerome Breen,David St Clair,Sian Caesar,Katherine Gordon-Smith,Lisa Jones,Christine Fraser,Elaine K. Green,Detelina Grozeva,Marian L. Hamshere,Peter Holmans,Ian Jones,George Kirov,Valentina Moskvina,Ivan Nikolov,Michael Conlon O'Donovan,Michael John Owen,David A. Collier,Amanda Elkin,Anne Farmer,Richard Williamson,Peter McGuffin,Allan H. Young,I. Nicol Ferrier,Stephen G. Ball,Anthony J. Balmforth,Jennifer H. Barrett,D. Timothy Bishop,Mark M. Iles,Azhar Maqbool,Nadira Yuldasheva,Alistair S. Hall,Peter S. Braund,Richard J. Dixon,Massimo Mangino,Suzanne Stevens,John R. Thompson,Francesca Bredin,Mark Tremelling,Miles Parkes,Hazel E. Drummond,Charlie W. Lees,Elaine R. Nimmo,Jack Satsangi,Sheila A. Fisher,Alastair Forbes,Cathryn M. Lewis,Clive M. Onnie,Natalie J. Prescott,Jeremy D. Sanderson,Christopher G. Mathew,Jamie Barbour,M. Khalid Mohiuddin,Catherine E. Todhunter,John C. Mansfield,Tariq Ahmad,Fraser Cummings,Derek P. Jewell,John Webster,Morris J. Brown,G. Mark Lathrop,John M. C. Connell,Anna F. Dominiczak,Carolina A. Braga Marcano,Beverley Burke,Richard Dobson,Johannie Gungadoo,Kate L. Lee,Patricia B. Munroe,Stephen Newhouse,Abiodun Onipinla,Chris Wallace,Mingzhan Xue,Mark J. Caulfield,Martin Farrall,Anne Barton,Ian N. Bruce,Hannah Donovan,Steve Eyre,Paul D. Gilbert,Samantha L. Hider,Anne Hinks,Sally John,Catherine Potter,Alan J. Silman,Deborah P M Symmons,Wendy Thomson,Jane Worthington,David B. Dunger,Barry Widmer,Timothy M. Frayling,Rachel M. Freathy,Hana Lango,John R. B. Perry,Beverley M. Shields,Michael N. Weedon,Andrew T. Hattersley,Graham A. Hitman,Mark Walker,Kate S. Elliott,Christopher J. Groves,Cecilia M. Lindgren,Nigel W. Rayner,Nicholas J. Timpson,Eleftheria Zeggini,Melanie J. Newport,Giorgio Sirugo,Emily J. Lyons,Fredrik O. Vannberg,Adrian V. S. Hill,Linda A. Bradbury,C Farrar,J J Pointon,Paul Wordsworth,Matthew A. Brown,Jayne A. Franklyn,Joanne M. Heward,Matthew J. Simmonds,Stephen C. L. Gough,Sheila Seal,Michael R. Stratton,Nazneen Rahman,Maria Ban,An Goris,Stephen Sawcer,Alastair Compston,David J. Conway,Muminatou Jallow,Kirk A. Rockett,Suzannah Bumpstead,Amy Chaney,Kate Downes,Mohammed J. R. Ghori,Rhian Gwilliam,Sarah E. Hunt,Michael Inouye,Andrew Keniry,Emma King,Ralph McGinnis,Simon C. Potter,Rathi Ravindrarajah,Pamela Whittaker,Claire Widden,David Withers,Niall Cardin,Teresa Ferreira,Joanne Pereira-Gale,Ingileif B. Hallgrímsdóttir,Bryan Howie,Zhan Su,Yik Ying Teo,Damjan Vukcevic,David Bentley,A Compston +195 more
TL;DR: This study has demonstrated that careful use of a shared control group represents a safe and effective approach to GWA analyses of multiple disease phenotypes; generated a genome-wide genotype database for future studies of common diseases in the British population; and shown that, provided individuals with non-European ancestry are excluded, the extent of population stratification in theBritish population is generally modest.
Journal Article
An integrated encyclopedia of DNA elements in the human genome.
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
Journal ArticleDOI
Finding the missing heritability of complex diseases
Teri A. Manolio,Francis S. Collins,Nancy J. Cox,David Goldstein,Lucia A. Hindorff,David J. Hunter,Mark I. McCarthy,Erin M. Ramos,Lon R. Cardon,Aravinda Chakravarti,Judy H. Cho,Alan E. Guttmacher,Augustine Kong,Leonid Kruglyak,Leonid Kruglyak,Elaine R. Mardis,Charles N. Rotimi,Montgomery Slatkin,David Valle,Alice S. Whittemore,Michael Boehnke,Andrew G. Clark,Evan E. Eichler,Greg Gibson,Jonathan L. Haines,Trudy F. C. Mackay,Steven A. McCarroll,Peter M. Visscher +27 more
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
Journal ArticleDOI
Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
Jean-Pierre Hugot,Mathias Chamaillard,Mathias Chamaillard,Habib Zouali,Suzanne Lesage,Jean-Pierre Cézard,Jacques Belaiche,Sven Almer,Curt Tysk,Colm O'Morain,Miquel A. Gassull,Vibeke Binder,Yigael Finkel,Antoine Cortot,Robert Modigliani,Pierre Laurent-Puig,C. Gower-Rousseau,J. Macry,Jean-Frederic Colombel,Mourad Sahbatou,Gilles Thomas,Gilles Thomas +21 more
TL;DR: It is suggested that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-kB in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn’s disease that can now be further investigated.
Related Papers (5)
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease
Luke Jostins,Stephan Ripke,Rinse K. Weersma,Richard H. Duerr,Dermot P.B. McGovern,Ken Y. Hui,James Lee,L. Philip Schumm,Yashoda Sharma,Carl A. Anderson,Jonah Essers,Mitja Mitrovic,Kaida Ning,Isabelle Cleynen,Emilie Theatre,Sarah L. Spain,Soumya Raychaudhuri,Philippe Goyette,Zhi Wei,Clara Abraham,Jean-Paul Achkar,Tariq Ahmad,Leila Amininejad,Ashwin N. Ananthakrishnan,Vibeke Andersen,Jane M. Andrews,Leonard Baidoo,Tobias Balschun,Peter A. Bampton,Alain Bitton,Gabrielle Boucher,Stephan Brand,Carsten Büning,Ariella Cohain,Sven Cichon,Mauro D'Amato,Dirk De Jong,Kathy L Devaney,Marla Dubinsky,Cathryn Edwards,David Ellinghaus,Lynnette R. Ferguson,Denis Franchimont,Karin Fransen,Richard B. Gearry,Michel Georges,Christian Gieger,Jürgen Glas,Talin Haritunians,Ailsa Hart,Christopher J. Hawkey,Matija Hedl,Xinli Hu,Tom H. Karlsen,Limas Kupčinskas,Subra Kugathasan,Anna Latiano,Debby Laukens,Ian C. Lawrance,Charlie W. Lees,Edouard Louis,Gillian Mahy,John C. Mansfield,Angharad R. Morgan,Craig Mowat,William G. Newman,Orazio Palmieri,Cyriel Y. Ponsioen,Uroš Potočnik,Natalie J. Prescott,Miguel Regueiro,Jerome I. Rotter,Richard K Russell,Jeremy D. Sanderson,Miquel Sans,Jack Satsangi,Stefan Schreiber,Lisa A. Simms,Jurgita Sventoraityte,Stephan R. Targan,Kent D. Taylor,Mark Tremelling,Hein W. Verspaget,Martine De Vos,Cisca Wijmenga,David C. Wilson,Juliane Winkelmann,Ramnik J. Xavier,Sebastian Zeissig,Bin Zhang,Clarence K. Zhang,Hongyu Zhao,Mark S. Silverberg,Vito Annese,Hakon Hakonarson,Steven R. Brant,Graham L. Radford-Smith,Christopher G. Mathew,John D. Rioux,Eric E. Schadt,Mark J. Daly,Andre Franke,Miles Parkes,Severine Vermeire,Jeffrey C. Barrett,Judy H. Cho +105 more
Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
Andre Franke,Dermot P.B. McGovern,Jeffrey C. Barrett,Kai Wang,Graham L. Radford-Smith,Tariq Ahmad,Charlie W. Lees,Tobias Balschun,James Lee,Rebecca L. Roberts,Carl A. Anderson,Joshua C. Bis,Suzanne Bumpstead,David Ellinghaus,Eleonora M. Festen,Michel Georges,Todd Green,Talin Haritunians,Luke Jostins,Anna Latiano,Christopher G. Mathew,Grant W. Montgomery,Natalie J. Prescott,Soumya Raychaudhuri,Jerome I. Rotter,Philip Schumm,Yashoda Sharma,Lisa A. Simms,Kent D. Taylor,David C. Whiteman,Cisca Wijmenga,Robert N. Baldassano,Murray L. Barclay,Theodore M. Bayless,Stephan Brand,Carsten Büning,Albert Cohen,Jean Frederick Colombel,Mario Cottone,Laura Stronati,Ted Denson,Martine De Vos,Renata D'Incà,Marla Dubinsky,Cathryn Edwards,Timothy H. Florin,Denis Franchimont,Richard B. Gearry,Jürgen Glas,Jürgen Glas,Jürgen Glas,André Van Gossum,Stephen L. Guthery,Jonas Halfvarson,Hein W. Verspaget,Jean-Pierre Hugot,Amir Karban,Debby Laukens,Ian C. Lawrance,Marc Lémann,Arie Levine,Cécile Libioulle,Edouard Louis,Craig Mowat,William G. Newman,Julián Panés,Anne M. Phillips,Deborah D. Proctor,Miguel Regueiro,Richard K Russell,Paul Rutgeerts,Jeremy D. Sanderson,Miquel Sans,Frank Seibold,A. Hillary Steinhart,Pieter C. F. Stokkers,Leif Törkvist,Gerd A. Kullak-Ublick,David C. Wilson,Thomas D. Walters,Stephan R. Targan,Steven R. Brant,John D. Rioux,Mauro D'Amato,Rinse K. Weersma,Subra Kugathasan,Anne M. Griffiths,John C. Mansfield,Severine Vermeire,Richard H. Duerr,Mark S. Silverberg,Jack Satsangi,Stefan Schreiber,Judy H. Cho,Vito Annese,Hakon Hakonarson,Mark J. Daly,Miles Parkes +97 more
PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses
Genetics of rheumatoid arthritis contributes to biology and drug discovery
Yukinori Okada,Yukinori Okada,Di Wu,Di Wu,Di Wu,Gosia Trynka,Gosia Trynka,Towfique Raj,Towfique Raj,Chikashi Terao,Katsunori Ikari,Yuta Kochi,Koichiro Ohmura,Akari Suzuki,Shinji Yoshida,Robert R. Graham,A. Manoharan,Ward Ortmann,Tushar Bhangale,Joshua C. Denny,Robert J. Carroll,Anne E. Eyler,Jeff Greenberg,Joel M. Kremer,Dimitrios A. Pappas,Lei Jiang,Jian Yin,Lingying Ye,Ding Feng Su,Jian Yang,Gang Xie,E.C. Keystone,Harm-Jan Westra,Tõnu Esko,Tõnu Esko,Tõnu Esko,Andres Metspalu,Xuezhong Zhou,Namrata Gupta,Daniel B. Mirel,Eli A. Stahl,Dorothee Diogo,Dorothee Diogo,Jing Cui,Jing Cui,Katherine P. Liao,Katherine P. Liao,Michael H. Guo,Michael H. Guo,Keiko Myouzen,Takahisa Kawaguchi,Marieke J H Coenen,Piet L. C. M. van Riel,Mart A F J van de Laar,Henk-Jan Guchelaar,Tom W J Huizinga,Philippe Dieudé,Xavier Mariette,S. Louis Bridges,Alexandra Zhernakova,Alexandra Zhernakova,René E. M. Toes,Paul P. Tak,Paul P. Tak,Paul P. Tak,Corinne Miceli-Richard,So Young Bang,Hye Soon Lee,Javier Martin,Miguel A. Gonzalez-Gay,Luis Rodriguez-Rodriguez,Solbritt Rantapää-Dahlqvist,Lisbeth Ärlestig,Hyon K. Choi,Hyon K. Choi,Yoichiro Kamatani,Pilar Galan,Mark Lathrop,Steve Eyre,Steve Eyre,John Bowes,John Bowes,Anne Barton,Niek de Vries,Larry W. Moreland,Lindsey A. Criswell,Elizabeth W. Karlson,Atsuo Taniguchi,Ryo Yamada,Michiaki Kubo,Jun Liu,Sang Cheol Bae,Jane Worthington,Jane Worthington,Leonid Padyukov,Lars Klareskog,Peter K. Gregersen,Soumya Raychaudhuri,Soumya Raychaudhuri,Barbara E. Stranger,Philip L. De Jager,Philip L. De Jager,Lude Franke,Peter M. Visscher,Matthew A. Brown,Hisashi Yamanaka,Tsuneyo Mimori,Atsushi Takahashi,Huji Xu,Timothy W. Behrens,Katherine A. Siminovitch,Shigeki Momohara,Fumihiko Matsuda,Kazuhiko Yamamoto,Robert M. Plenge,Robert M. Plenge +115 more
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