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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Germline Features Associated with Immune Infiltration in Solid Tumors
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TL;DR: Overall, multiple germline genetic features associated with tumor-immune phenotypes are identified and a framework for probing inherited features that contribute to differences in immune infiltration is developed.
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Significant variation between SNP-based HLA imputations in diverse populations: the last mile is the hardest.
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Progress and promise in understanding the genetic basis of common diseases
TL;DR: In this article, the authors describe the technological and analytical advances that have enabled genome-wide association studies to be successful in identifying a large number of genetic variants robustly associated with common disease.
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Common polygenic variation in coeliac disease and confirmation of ZNF335 and NIFA as disease susceptibility loci.
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TL;DR: In the largest association analysis of CD to date, 39 non-HLA risk loci were identified, 13 of which were new, in a sample of 12 014 individuals with CD and 12 228 controls using the Immunochip genotyping platform.
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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.
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.
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