1. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
- Author
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Raj T, Rothamel K, Mostafavi S, Ye C, Lee MN, Replogle JM, Feng T, Lee M, Asinovski N, Frohlich I, Imboywa S, Von Korff A, Okada Y, Patsopoulos NA, Davis S, McCabe C, Paik HI, Srivastava GP, Raychaudhuri S, Hafler DA, Koller D, Regev A, Hacohen N, Mathis D, Benoist C, Stranger BE, and De Jager PL
- Subjects
- Adaptive Immunity genetics, Alleles, Alzheimer Disease ethnology, Alzheimer Disease genetics, Autoimmune Diseases ethnology, Ethnicity genetics, Genetic Predisposition to Disease ethnology, Genome-Wide Association Study, Humans, Immunity, Innate genetics, Multiple Sclerosis ethnology, Multiple Sclerosis genetics, Neurodegenerative Diseases ethnology, Parkinson Disease ethnology, Parkinson Disease genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Rheumatic Fever ethnology, Rheumatic Fever genetics, Transcriptome, Autoimmune Diseases genetics, Autoimmunity genetics, CD4-Positive T-Lymphocytes immunology, Genetic Predisposition to Disease genetics, Monocytes immunology, Neurodegenerative Diseases genetics
- Abstract
To extend our understanding of the genetic basis of human immune function and dysfunction, we performed an expression quantitative trait locus (eQTL) study of purified CD4(+) T cells and monocytes, representing adaptive and innate immunity, in a multi-ethnic cohort of 461 healthy individuals. Context-specific cis- and trans-eQTLs were identified, and cross-population mapping allowed, in some cases, putative functional assignment of candidate causal regulatory variants for disease-associated loci. We note an over-representation of T cell-specific eQTLs among susceptibility alleles for autoimmune diseases and of monocyte-specific eQTLs among Alzheimer's and Parkinson's disease variants. This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants.
- Published
- 2014
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