Complex genetic signatures in immune cells underlie autoimmunity and inform therapy.
Complex genetic signatures in immune cells underlie autoimmunity and inform therapy.
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免疫细胞中自身免疫和疗法的复杂遗传特征。
DOI：
10.1038/s41588-020-0684-4
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发表时间：
2020-10
期刊：
影响因子：
30.8
通讯作者：
Cucca F
中科院分区：
文献类型：
--
作者：
Orrù V;Steri M;Sidore C;Marongiu M;Serra V;Olla S;Sole G;Lai S;Dei M;Mulas A;Virdis F;Piras MG;Lobina M;Marongiu M;Pitzalis M;Deidda F;Loizedda A;Onano S;Zoledziewska M;Sawcer S;Devoto M;Gorospe M;Abecasis GR;Floris M;Pala M;Schlessinger D;Fiorillo E;Cucca F
我们报告了约2200万个变异对3757名撒丁人的731个免疫细胞特征的影响。我们在70个位点（其中53个是新发现的）的459个细胞性状中检测到122个显著的（P < 1.28 × 10−11）独立关联信号，确定了参与细胞调控的几种分子和机制。此外，36个位点的53个信号与先前报道的疾病相关信号重叠，主要用于自身免疫性疾病，突出了发病机制中的中间表型。总的来说，我们的研究结果说明了免疫细胞在细胞亚型水平上对自身免疫性疾病风险具有高度选择性作用的复杂遗传调控。这些结果确定了药物靶向途径，为设计更特异性的自身免疫性疾病治疗提供了信息。
We report on the influence of ~22 million variants on 731 immune cell traits in a cohort of 3,757 Sardinians. We detected 122 significant (P < 1.28 × 10−11) independent association signals for 459 cell traits at 70 loci (53 of them novel) identifying several molecules and mechanisms involved in cell regulation. Furthermore, 53 signals at 36 loci overlapped with previously reported disease-associated signals, predominantly for autoimmune disorders, highlighting intermediate phenotypes in pathogenesis. Collectively, our findings illustrate complex genetic regulation of immune cells with highly selective effects on autoimmune disease risk at the cell-subtype level. These results identify drug-targetable pathways informing the design of more specific treatments for autoimmune diseases.
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影响因子：
30.8
作者：
Hinks, Anne;Cobb, Joanna;Marion, Miranda C.;Prahalad, Sampath;Sudman, Marc;Bowes, John;Martin, Paul;Comeau, Mary E.;Sajuthi, Satria;Andrews, Robert;Brown, Milton;Chen, Wei-Min;Concannon, Patrick;Deloukas, Panos;Edkins, Sarah;Eyre, Stephen;Gaffney, Patrick M.;Guthery, Stephen L.;Guthridge, Joel M.;Hunt, Sarah E.;James, Judith A.;Keddache, Mehdi;Moser, Kathy L.;Nigrovic, Peter A.;Onengut-Gumuscu, Suna;Onslow, Mitchell L.;Rose, Carlos D.;Rich, Stephen S.;Steel, Kathryn J. A.;Wakeland, Edward K.;Wallace, Carol A.;Wedderburn, Lucy R.;Woo, Patricia;Bohnsack, John F.;Haas, Johannes Peter;Glass, David N.;Langefeld, Carl D.;Thomson, Wendy;Thompson, Susan D.
通讯作者：
Thompson, Susan D.
影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
影响因子：
30.8
作者：
Ellinghaus D;Jostins L;Spain SL;Cortes A;Bethune J;Han B;Park YR;Raychaudhuri S;Pouget JG;Hübenthal M;Folseraas T;Wang Y;Esko T;Metspalu A;Westra HJ;Franke L;Pers TH;Weersma RK;Collij V;D'Amato M;Halfvarson J;Jensen AB;Lieb W;Degenhardt F;Forstner AJ;Hofmann A;International IBD Genetics Consortium (IIBDGC);International Genetics of Ankylosing Spondylitis Consortium (IGAS);International PSC Study Group (IPSCSG);Genetic Analysis of Psoriasis Consortium (GAPC);Psoriasis Association Genetics Extension (PAGE);Schreiber S;Mrowietz U;Juran BD;Lazaridis KN;Brunak S;Dale AM;Trembath RC;Weidinger S;Weichenthal M;Ellinghaus E;Elder JT;Barker JN;Andreassen OA;McGovern DP;Karlsen TH;Barrett JC;Parkes M;Brown MA;Franke A
通讯作者：
Franke A
影响因子：
64.5
作者：
Brodin P;Jojic V;Gao T;Bhattacharya S;Angel CJ;Furman D;Shen-Orr S;Dekker CL;Swan GE;Butte AJ;Maecker HT;Davis MM
通讯作者：
Davis MM
影响因子：
30.8
作者：
Fortune MD;Guo H;Burren O;Schofield E;Walker NM;Ban M;Sawcer SJ;Bowes J;Worthington J;Barton A;Eyre S;Todd JA;Wallace C
通讯作者：
Wallace C