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

作者：Towfique Raj, Katie Rothamel, Sara Mostafavi, Chun Jimmie Ye, Mark N. Lee, Joseph M. Replogle, Ting Feng, Michelle Hyunju Lee, Natasha Asinovski, Irene Y. Frohlich, Selina H. Imboywa, Alina Von Korff, Yukinori Okada, Nikolaos A. Patsopoulos, Scott P. Davis, Cristin McCabe, Hyun-il Paik, Gyan Prakash Srivastava, Soumya Raychaudhuri, David A. Hafler, Daphne Koller, Aviv Regev, Nir Hacohen, Diane J. Mathis, Christophe O. Benoist, Barbara E. Stranger, Philip L. De Jager · 发表于：Science · 年份：2014 · DOI：10.1126/science.1249547 · 被引用次数：574 · 研究领域：T-cell and B-cell Immunology、Single-cell and spatial transcriptomics、Genetic Associations and Epidemiology

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.