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A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1
A. Strange,Francesca Capon,C. C. A. Spencer,Joanne Knight,Michael E. Weale,Michael H. Allen,Anne Barton,Céline Bellenguez,Judith G.M. Bergboer,J. M. BlackweL,Elvira Bramon,Suzannah Bumpstead,Juan P. Casas,Michael J. Cork,Aiden Corvin,Panagiotis Deloukas,Alexander T. Dilthey,Audrey Duncanson,Sarah Edkins,X. EstiviL,Oliver FitzGerald,C. FrEman,Emiliano Giardina,Emma Gray,Angelika Hofer,Ulrike Hüffmeier,Sarah E. Hunt,Alan D. Irvine,Janusz Jankowski,Brian Kirby,Cordelia Langford,Jesús Lascorz,Joyce Leman,Stephen Leslie,L. MaLbris,Hugh S. Markus,Christopher G. Mathew,Whi McLean,Ross McManus,R. MöSner,Loukas Moutsianas,Åsa Torinsson Naluai,Frank O. Nestle,G. NoveLi,Alexandros Onoufriadis,Colin N. A. Palmer,Carlo Perricone,Matti Pirinen,Robert Plomin,S. C. PoTer,Ramon M. Pujol,Anna Rautanen,Eva Riveira-Muñoz,Anthony W. Ryan,Wolfgang Salmhofer,L. SamuelSon,Stephen Sawcer,Joost Schalkwijk,Catherine H. Smith,Mona Ståhle,Zhan Su,Rachid Tazi-Ahnini,Heiko Traupe,Ananth C. Viswanathan,Richard B. Warren,Wolfgang Weger,Katarina Wolk,N. Wod,Jane Worthington,Helen S. Young,Patrick L.J.M. Zeeuwen,Adrian Hayday,A D Burden,Christopher E.M. Griffiths,Juha Kere,André Reis,Gil McVean,David M. Evans,Matthew A. Brown,J. Barker,Leena Peltonen,P. Donely,Richard C. Trembath +82 more
- 17 Oct 2010
773
TL;DR: In this article, a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls was conducted.
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Abstract: To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P < 5-10 -8 and two loci with a combined P < 5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis.
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Intersection of population variation and autoimmunity genetics in human T cell activation
Chun Jimmie Ye,Ting Feng,Ho Keun Kwon,Towfique Raj,Towfique Raj,Michael T. Wilson,Natasha Asinovski,Cristin McCabe,Cristin McCabe,Michelle Lee,Irene Frohlich,Hyun Il Paik,Noah Zaitlen,Nir Hacohen,Barbara E. Stranger,Philip L. De Jager,Philip L. De Jager,Diane Mathis,Diane Mathis,Aviv Regev,Aviv Regev,Christophe Benoist,Christophe Benoist +22 more
TL;DR: The ImmVar project as mentioned in this paper performed a rigorously controlled analysis of the responses of human blood CD4+ T cells to activation in unbiased conditions or in a culture regimen that promotes differentiation to the T helper 17 cell (TH17) phenotype.
Current knowledge on psoriasis and autoimmune diseases.
TL;DR: Common cellular pathways and participants that mediate psoriasis and other autoimmune disorders that share these cellular signaling pathways are discussed.
The Causes and Consequences of Genetic Interactions (Epistasis)
TL;DR: An overview of the current understanding of the mechanisms causing epistasis at the molecular level, the consequences of genetic interactions for evolution and genetic prediction, and the applications of epistasis for understanding biology and determining macromolecular structures is provided.
235
Detection and replication of epistasis influencing transcription in humans
Gibran Hemani,Konstantin Shakhbazov,Harm-Jan Westra,Tõnu Esko,Anjali K. Henders,Allan F. McRae,Jian Yang,Greg Gibson,Nicholas G. Martin,Andres Metspalu,Lude Franke,Grant W. Montgomery,Peter M. Visscher,Joseph E. Powell +13 more
TL;DR: This study presents the first evidence, to the knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.
Negligible impact of rare autoimmune-locus coding-region variants on missing heritability
Karen A. Hunt,Vanisha Mistry,Nicholas A. Bockett,Tariq Ahmad,Maria Ban,Jonathan Barker,Jeffrey C. Barrett,Hannah Blackburn,Oliver J. Brand,Oliver S. Burren,Francesca Capon,Alastair Compston,Stephen C. L. Gough,Luke Jostins,Yong Kong,James Lee,Monkol Lek,Daniel G. MacArthur,John C. Mansfield,Christopher G. Mathew,Charles A. Mein,Muddassar M. Mirza,Sarah Nutland,Suna Onengut-Gumuscu,Efterpi Papouli,Miles Parkes,Stephen S. Rich,Steven Sawcer,Jack Satsangi,Matthew J. Simmonds,Richard C. Trembath,Neil Walker,Eva Wozniak,John A. Todd,Michael A. Simpson,Vincent Plagnol,David A. van Heel +36 more
TL;DR: The data indicate that the missing heritability for common autoimmune diseases may not be attributable to the rare coding-region variant portion of the allelic spectrum, but perhaps, as others have proposed, may be a result of many common-variant loci of weak effect.
References
Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
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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.
A new statistical method for haplotype reconstruction from population data.
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