Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
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DOI：
10.1126/science.1249547
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发表时间：
2014-05-02
期刊：
影响因子：
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通讯作者：
De Jager PL
中科院分区：
文献类型：
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作者：
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;De Jager PL
为了扩展我们对人类免疫功能和功能障碍的遗传基础的理解，我们在461名健康个体的多种族队列中对纯化的CD4+ T细胞和单核细胞（代表适应性和先天性免疫）进行了表达数量性状位点（eQTL）研究。背景特异性的顺式和反式eQTL被确定，交叉群体作图允许，在某些情况下，推定的功能分配的候选致病调控变异的疾病相关基因座。我们注意到T细胞特异性eQTL在自身免疫性疾病的易感等位基因中的过度表达，以及单核细胞特异性eQTL在阿尔茨海默病和帕金森病变体中的过度表达。这种极化暗示了这些疾病中的特定免疫细胞类型，并指出需要识别疾病易感性变体的细胞自主效应。
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.