CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits.
CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits.
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DOI：
10.1186/1756-0381-7-21
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发表时间：
2014
期刊：
影响因子：
4.5
通讯作者：
Ordovás JM
中科院分区：
文献类型：
--
作者：
Parnell LD;Blokker BA;Dashti HS;Nesbeth PD;Cooper BE;Ma Y;Lee YC;Hou R;Lai CQ;Richardson K;Ordovás JM
在过去的十年里，对复杂性状的遗传理解有了很大的发展，但仍然受到对表型变异的不完全描述的阻碍。基因-环境(GxE)的相互作用是这些因素之一，并且以饮食和体力活动为幌子，是心脏代谢表型和随后的疾病的重要调节者。我们挖掘科学文献，从386篇关于血脂、血糖特征、肥胖人体测量学、血管测量、炎症和代谢综合征的出版物中收集GxE的交互作用，并介绍了一种基因-环境交互资源--心脏GxE。然后，我们分析了支持心脏代谢性GxE的基因和SNPs，以证明GxE SNPs的用途，并识别这些重要遗传变异的特征。我们能够从我们对GxE的广泛分析中得出许多观察结果。1)心脏GxE基因SNPs与主效GWA型变异的重叠较少，表明环境与遗传因素的交互作用对心脏代谢性状的重要性。2)这些GxE SNP丰富了对气候和地理特征的适应，影响了能量平衡和对体力活动的反应。3)对血浆胆固醇降低或动脉粥样硬化斑块消退的基因网络的比较表明，GxE基因在这些反应中发挥着更大的作用，特别是通过高能量饮食和脂肪摄取，而不是GWAS鉴定的相同性状的基因。还探讨了心脏GxE数据集的其他方面。总体而言，我们证明了支持心脏代谢GxE相互作用的SNPs通常表现出转录效应或处于正选择状态。尽管如此，并不是所有这样的SNP都可以经常被分配到潜在的功能或调节角色，因为缺乏特定细胞类型的数据，或者缺乏接近GxE环境因素的治疗数据。随着对代谢相关复杂疾病风险的研究开始进行全基因组GxE相互作用测试，心脏GxE将是一个有用的资源。
Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases. We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored. Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related complex disease risk embarking on genome-wide GxE interaction tests, CardioGxE will be a useful resource.
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影响因子：
4.5
作者：
Hancock, Angela M.;Witonsky, David B.;Gordon, Adam S.;Eshel, Gidon;Pritchard, Jonathan K.;Coop, Graham;Di Rienzo, Anna
通讯作者：
Di Rienzo, Anna
影响因子：
4.4
作者：
Bruno AE;Li L;Kalabus JL;Pan Y;Yu A;Hu Z
通讯作者：
Hu Z
影响因子：
--
作者：
AlSaleh, Aseel;Frost, Gary S.;O'Dell, Sandra D.
通讯作者：
O'Dell, Sandra D.
影响因子：
4.5
作者：
Innocenti F;Cooper GM;Stanaway IB;Gamazon ER;Smith JD;Mirkov S;Ramirez J;Liu W;Lin YS;Moloney C;Aldred SF;Trinklein ND;Schuetz E;Nickerson DA;Thummel KE;Rieder MJ;Rettie AE;Ratain MJ;Cox NJ;Brown CD
通讯作者：
Brown CD
解偶联蛋白的群体遗传分析支持 UCP3 在人类抗寒性中的作用。
影响因子：
10.7
作者：
Hancock AM;Clark VJ;Qian Y;Di Rienzo A
通讯作者：
Di Rienzo A