Polarization of the Effects of Autoimmune and Neurodegenerative Risk Alleles in Leukocytes

• Published in: Science (American Association for the Advancement of Science) Vol. 344; no. 6183; pp. 519 - 523
• Main Authors: Raj, Towfique, Rothamel, Katie, Mostafavi, Sara, Ye, Chun, Lee, Mark N., Replogle, Joseph M., Feng, Ting, Lee, Michelle, Asinovski, Natasha, Frohlich, Irene, Imboywa, Selina, Von Korff, Alina, Okada, Yukinori, Patsopoulos, Nikolaos A., Davis, Scott, McCabe, Cristin, Paik, Hyun-il, Srivastava, Gyan P., Raychaudhuri, Soumya, Hafler, David A., Koller, Daphne, Regev, Aviv, Hacohen, Nir, Mathis, Diane, Benoist, Christophe, Stranger, Barbara E., De Jager, Philip L.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 02-05-2014; The American Association for the Advancement of Science
• Subjects: Adaptive Immunity - genetics; Alleles; Alzheimer Disease - ethnology; Alzheimer Disease - genetics; Alzheimers disease; Autoimmune diseases; Autoimmune Diseases - ethnology; Autoimmune Diseases - genetics; Autoimmunity - genetics; CD4-Positive T-Lymphocytes - immunology; Ethnicity - genetics; Gene expression; Gene loci; Genes; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genetics; Genome-Wide Association Study; Humans; Immunity, Innate - genetics; Immunology; Leukocytes; Monocytes; Monocytes - immunology; Multiple Sclerosis - ethnology; Multiple Sclerosis - genetics; Nervous system diseases; Neurodegenerative diseases; Neurodegenerative Diseases - ethnology; Neurodegenerative Diseases - genetics; Neurological disorders; Parkinson Disease - ethnology; Parkinson Disease - genetics; Phenotypic traits; Polymorphism, Single Nucleotide; Population genetics; Quantitative Trait Loci; Rheumatic Fever - ethnology; Rheumatic Fever - genetics; Ribonucleic acid; RNA; T lymphocytes; Transcriptome
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1249547

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.