Transancestral mapping and genetic load in systemic lupus erythematosus.
Transancestral mapping and genetic load in systemic lupus erythematosus.
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DOI：
10.1038/ncomms16021
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发表时间：
2017-07-17
影响因子：
16.6
通讯作者：
Vyse TJ
中科院分区：
文献类型：
--
作者：
Langefeld CD;Ainsworth HC;Cunninghame Graham DS;Kelly JA;Comeau ME;Marion MC;Howard TD;Ramos PS;Croker JA;Morris DL;Sandling JK;Almlöf JC;Acevedo-Vásquez EM;Alarcón GS;Babini AM;Baca V;Bengtsson AA;Berbotto GA;Bijl M;Brown EE;Brunner HI;Cardiel MH;Catoggio L;Cervera R;Cucho-Venegas JM;Dahlqvist SR;D'Alfonso S;Da Silva BM;de la Rúa Figueroa I;Doria A;Edberg JC;Endreffy E;Esquivel-Valerio JA;Fortin PR;Freedman BI;Frostegård J;García MA;de la Torre IG;Gilkeson GS;Gladman DD;Gunnarsson I;Guthridge JM;Huggins JL;James JA;Kallenberg CGM;Kamen DL;Karp DR;Kaufman KM;Kottyan LC;Kovács L;Laustrup H;Lauwerys BR;Li QZ;Maradiaga-Ceceña MA;Martín J;McCune JM;McWilliams DR;Merrill JT;Miranda P;Moctezuma JF;Nath SK;Niewold TB;Orozco L;Ortego-Centeno N;Petri M;Pineau CA;Pons-Estel BA;Pope J;Raj P;Ramsey-Goldman R;Reveille JD;Russell LP;Sabio JM;Aguilar-Salinas CA;Scherbarth HR;Scorza R;Seldin MF;Sjöwall C;Svenungsson E;Thompson SD;Toloza SMA;Truedsson L;Tusié-Luna T;Vasconcelos C;Vilá LM;Wallace DJ;Weisman MH;Wither JE;Bhangale T;Oksenberg JR;Rioux JD;Gregersen PK;Syvänen AC;Rönnblom L;Criswell LA;Jacob CO;Sivils KL;Tsao BP;Schanberg LE;Behrens TW;Silverman ED;Alarcón-Riquelme ME;Kimberly RP;Harley JB;Wakeland EK;Graham RR;Gaffney PM;Vyse TJ
系统性红斑狼疮（SLE）是一种自身免疫性疾病，具有明显的性别和种族差异。我们报告了一项大型的SLE跨祖关联研究，使用来自欧洲（EA），非洲（AA）和西班牙美洲印第安人（HA）血统的27,574例个体的免疫芯片基因型数据。我们在EA中鉴定出58个不同的非HLA区域，在AA中鉴定出9个，在HA中鉴定出16个（这些区域中约50%具有多个独立的关联）;其中包括24个新的SLE区域（P<5 × 10−8），在已建立的区域中精确的关联信号，与其他祖先的扩展关联，以及解开的复杂HLA多基因效应。危险等位基因计数（遗传负荷）显示出SLE风险的加速模式，这使我们对自身免疫性疾病的累积命中假说提出质疑。通过比较三个家系的结果，可以确定SLE风险的家系依赖性和家系独立性。我们的研究结果与采样人群的独特和复杂的历史相一致，并共同帮助澄清SLE的遗传结构和种族差异。系统性红斑狼疮（SLE）是一种自身免疫性疾病，具有强烈的种族和性别偏见。在一项跨祖遗传关联研究中，Langefeld等人鉴定了24个与狼疮风险相关的新区域，并提出了一个累积命中假设，用于赋予SLE风险的基因座。
Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10−8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE. Systemic lupus erythematosus (SLE) is an autoimmune disease with a strong ethnic and gender bias. In a transancestral genetic association study, Langefeld et al. identify 24 novel regions associated with risk to lupus and propose a cumulative hits hypothesis for loci conferring risk to SLE.
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影响因子：
3.7
作者：
Jia X;Zha T;Wu B;Zhang Y;Chen W;Wang X;Yu H;He G
通讯作者：
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de Bakker, Paul I. W.
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