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
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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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Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.
TL;DR: The MR-PRESSO test detects and corrects horizontal pleiotropy in multi-instrument Mendelian randomization (MR) analyses and introduces distortions in the causal estimates in MR that ranged on average from –131% to 201%; it is shown using simulations that the MR-pressO test is best suited when horizontal Pleiotropy occurs in <50% of instruments.
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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
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The evolving landscape of biomarkers for checkpoint inhibitor immunotherapy
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References
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