Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.
Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci.
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腹主动脉瘤的全基因组关联研究的荟萃分析确定了四个新的疾病特异性风险基因座。
DOI：
10.1161/circresaha.116.308765
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发表时间：
2017-01-20
影响因子：
20.1
通讯作者：
Bown MJ
中科院分区：
文献类型：
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作者：
Jones GT;Tromp G;Kuivaniemi H;Gretarsdottir S;Baas AF;Giusti B;Strauss E;Van't Hof FN;Webb TR;Erdman R;Ritchie MD;Elmore JR;Verma A;Pendergrass S;Kullo IJ;Ye Z;Peissig PL;Gottesman O;Verma SS;Malinowski J;Rasmussen-Torvik LJ;Borthwick KM;Smelser DT;Crosslin DR;de Andrade M;Ryer EJ;McCarty CA;Böttinger EP;Pacheco JA;Crawford DC;Carrell DS;Gerhard GS;Franklin DP;Carey DJ;Phillips VL;Williams MJ;Wei W;Blair R;Hill AA;Vasudevan TM;Lewis DR;Thomson IA;Krysa J;Hill GB;Roake J;Merriman TR;Oszkinis G;Galora S;Saracini C;Abbate R;Pulli R;Pratesi C;Saratzis A;Verissimo AR;Bumpstead S;Badger SA;Clough RE;Cockerill G;Hafez H;Scott DJ;Futers TS;Romaine SP;Bridge K;Griffin KJ;Bailey MA;Smith A;Thompson MM;van Bockxmeer FM;Matthiasson SE;Thorleifsson G;Thorsteinsdottir U;Blankensteijn JD;Teijink JA;Wijmenga C;de Graaf J;Kiemeney LA;Lindholt JS;Hughes A;Bradley DT;Stirrups K;Golledge J;Norman PE;Powell JT;Humphries SE;Hamby SE;Goodall AH;Nelson CP;Sakalihasan N;Courtois A;Ferrell RE;Eriksson P;Folkersen L;Franco-Cereceda A;Eicher JD;Johnson AD;Betsholtz C;Ruusalepp A;Franzén O;Schadt EE;Björkegren JL;Lipovich L;Drolet AM;Verhoeven EL;Zeebregts CJ;Geelkerken RH;van Sambeek MR;van Sterkenburg SM;de Vries JP;Stefansson K;Thompson JR;de Bakker PI;Deloukas P;Sayers RD;Harrison SC;van Rij AM;Samani NJ;Bown MJ
补充数字内容可在文本中找到。腹主动脉瘤（AAA）是一种复杂的疾病，遗传和环境的危险因素。总之，6个先前确定的风险位点只能解释AAA遗传性的一小部分。使用所有可用的全基因组关联研究数据确定其他AAA风险位点。通过对6个全基因组关联研究数据集的荟萃分析和总计10204例病例和107766例对照的验证研究，我们确定了4个新的AAA风险位点：1q32.3（SMYD 2），13q12.11（LINC 00540），20q13.12（靠近PCIF 1/MMP 9/ZNF 335）和21q22.2（ERG）。在各种数据库检索中，我们没有观察到AAA单核苷酸多态性与冠状动脉疾病、血压、血脂或糖尿病之间的新关联。网络分析确定ERG，IL 6 R和LDLR作为MMP 9的修饰剂，ERG和MMP 9之间存在直接相互作用。与其他心血管疾病和相关特征相比，AAA的4个新风险位点似乎对AAA具有特异性，这表明传统的心血管风险因素管理在预防动脉瘤疾病进展方面可能价值有限。
Supplemental Digital Content is available in the text. Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. To identify additional AAA risk loci using data from all available genome-wide association studies. Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.