Mendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease.
Mendelian randomization and pathway analysis demonstrate shared genetic associations between lupus and coronary artery disease.
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DOI：
10.1016/j.xcrm.2022.100805
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发表时间：
2022-11-15
影响因子：
14.3
通讯作者：
Lipsky, Peter E.
中科院分区：
文献类型：
--
作者：
Kain, Jessica;Owen, Katherine A.;Marion, Miranda C.;Langefeld, Carl D.;Grammer, Amrie C.;Lipsky, Peter E.
冠状动脉疾病（CAD）是系统性红斑狼疮（SLE）患者死亡的主要原因。尽管临床证据支持SLE和CAD之间的关联，但多效性调整的遗传关联研究有限，仅关注少数常见风险位点。在这里，我们通过传统的孟德尔随机化（MR）方法确定了SLE相关的非HLA SNP对CAD的净正因果关系估计。使用SNP到基因映射的途径分析，然后基于蛋白质-蛋白质相互作用（PPI）的无监督聚类，识别由阳性和阴性因果基因集组成的生物网络。此外，我们确认的因果关系的特定SNP基因模块对CAD仅使用SNP映射到每个PPI定义的功能基因集作为工具变量。这种基于PPI的MR方法阐明了SLE和CAD之间具有因果关系的各种分子途径，并确定了可能导致这两种病理的生物学途径，揭示了用于管理SLE中CAD的已知和新型治疗干预措施。SLE的遗传易感性导致CAD风险增加SLE中CVD风险增加涉及动脉粥样硬化而不是心功能障碍基于PPI的MR识别SLE和CAD之间因果关系的途径途径分析为SLE中CAD的治疗选择提供信息Kain et al.使用传统和综合的孟德尔随机化（MR）方法报告SLE和CAD之间的正遗传关系。MR分析结合网络建模突出了这两种疾病的共同遗传风险，并确定了参与SLE CAD发展的假定分子途径。
Coronary artery disease (CAD) is a leading cause of death in patients with systemic lupus erythematosus (SLE). Despite clinical evidence supporting an association between SLE and CAD, pleiotropy-adjusted genetic association studies are limited and focus on only a few common risk loci. Here, we identify a net positive causal estimate of SLE-associated non-HLA SNPs on CAD by traditional Mendelian randomization (MR) approaches. Pathway analysis using SNP-to-gene mapping followed by unsupervised clustering based on protein-protein interactions (PPIs) identifies biological networks composed of positive and negative causal sets of genes. In addition, we confirm the casual effects of specific SNP-to-gene modules on CAD using only SNP mapping to each PPI-defined functional gene set as instrumental variables. This PPI-based MR approach elucidates various molecular pathways with causal implications between SLE and CAD and identifies biological pathways likely causative of both pathologies, revealing known and novel therapeutic interventions for managing CAD in SLE. Genetic predisposition to SLE confers risk of CAD Increased CVD risk in SLE involves atherosclerosis rather than cardiac dysfunction PPI-based MR identifies pathways with causal implications between SLE and CAD Pathway analysis informs therapeutic selection for managing CAD in SLE Kain et al. report a positive genetic relationship between SLE and CAD using traditional and comprehensive Mendelian randomization (MR) approaches. MR analysis coupled with network modeling highlights the shared genetic risk underlying the two diseases and identifies putative molecular pathways involved in the development of CAD in SLE.
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影响因子：
3.9
作者：
Ajeganova S;Hafström I;Frostegård J
通讯作者：
Frostegård J
DOI：
10.1002/art.39403
发表时间：
2016-01
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
--
作者：
Demirci FY;Wang X;Kelly JA;Morris DL;Barmada MM;Feingold E;Kao AH;Sivils KL;Bernatsky S;Pineau C;Clarke AE;Ramsey-Goldman R;Vyse TJ;Gaffney PM;Manzi S;Kamboh MI
通讯作者：
Kamboh MI
影响因子：
30.8
作者：
Finucane HK;Bulik-Sullivan B;Gusev A;Trynka G;Reshef Y;Loh PR;Anttila V;Xu H;Zang C;Farh K;Ripke S;Day FR;ReproGen Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium;RACI Consortium;Purcell S;Stahl E;Lindstrom S;Perry JR;Okada Y;Raychaudhuri S;Daly MJ;Patterson N;Neale BM;Price AL
通讯作者：
Price AL
影响因子：
30.8
作者：
Howson JMM;Zhao W;Barnes DR;Ho WK;Young R;Paul DS;Waite LL;Freitag DF;Fauman EB;Salfati EL;Sun BB;Eicher JD;Johnson AD;Sheu WHH;Nielsen SF;Lin WY;Surendran P;Malarstig A;Wilk JB;Tybjærg-Hansen A;Rasmussen KL;Kamstrup PR;Deloukas P;Erdmann J;Kathiresan S;Samani NJ;Schunkert H;Watkins H;CARDIoGRAMplusC4D;Do R;Rader DJ;Johnson JA;Hazen SL;Quyyumi AA;Spertus JA;Pepine CJ;Franceschini N;Justice A;Reiner AP;Buyske S;Hindorff LA;Carty CL;North KE;Kooperberg C;Boerwinkle E;Young K;Graff M;Peters U;Absher D;Hsiung CA;Lee WJ;Taylor KD;Chen YH;Lee IT;Guo X;Chung RH;Hung YJ;Rotter JI;Juang JJ;Quertermous T;Wang TD;Rasheed A;Frossard P;Alam DS;Majumder AAS;Di Angelantonio E;Chowdhury R;EPIC-CVD;Chen YI;Nordestgaard BG;Assimes TL;Danesh J;Butterworth AS;Saleheen D
通讯作者：
Saleheen D
中国汉族人群的全基因组关联研究确定了系统性红斑狼疮的九个新易感位点
影响因子：
30.8
作者：
Han, Jian-Wen;Zheng, Hou-Feng;Zhang, Xue-Jun
通讯作者：
Zhang, Xue-Jun