Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.
Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.
复制标题
使用密集的插图地图发现与与心脏代谢风险相关的遗传基因座的发现和完善。
DOI：
10.1038/ng.3668
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发表时间：
2016-11
期刊：
影响因子：
30.8
通讯作者：
Soranzo N
中科院分区：
文献类型：
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作者：
Iotchkova V;Huang J;Morris JA;Jain D;Barbieri C;Walter K;Min JL;Chen L;Astle W;Cocca M;Deelen P;Elding H;Farmaki AE;Franklin CS;Franberg M;Gaunt TR;Hofman A;Jiang T;Kleber ME;Lachance G;Luan J;Malerba G;Matchan A;Mead D;Memari Y;Ntalla I;Panoutsopoulou K;Pazoki R;Perry JRB;Rivadeneira F;Sabater-Lleal M;Sennblad B;Shin SY;Southam L;Traglia M;van Dijk F;van Leeuwen EM;Zaza G;Zhang W;UK10K Consortium;Amin N;Butterworth A;Chambers JC;Dedoussis G;Dehghan A;Franco OH;Franke L;Frontini M;Gambaro G;Gasparini P;Hamsten A;Issacs A;Kooner JS;Kooperberg C;Langenberg C;Marz W;Scott RA;Swertz MA;Toniolo D;Uitterlinden AG;van Duijn CM;Watkins H;Zeggini E;Maurano MT;Timpson NJ;Reiner AP;Auer PL;Soranzo N
大规模的全基因组序列数据集提供了新的机会，以确定人类特征的遗传变异。在这里，我们基于UK 10 K和1000个基因组计划的全基因组序列数据对35，981名欧洲血统的研究参与者进行基因型插补，然后与20个定量心脏代谢和血液学特征进行关联分析。我们描述了17种新的关联，包括6种罕见（次要等位基因频率[MAF]<1%）或低频变异（1%<MAF<5%）与血小板计数（PLT），红细胞指数（MCH，MCV）和高密度脂蛋白（HDL）胆固醇。应用精细映射分析233个已知的和新的基因座与20个性状，我们解决了59个基因座的关联，可信的20个或更少的变异，并描述了预测的调控功能区域内的性状富集。这些发现增强了对心脏代谢和血液病风险因素的等位基因结构的理解，并通过鉴定潜在的新型生物靶点提供了额外的功能性见解。
Large-scale whole genome sequence datasets offer novel opportunities to identify genetic variation underlying human traits. Here we apply genotype imputation based on whole genome sequence data from the UK10K and the 1000 Genomes Projects into 35,981 study participants of European ancestry, followed by association analysis with twenty quantitative cardiometabolic and hematologic traits. We describe 17 novel associations, including six rare (minor allele frequency [MAF]<1%) or low frequency variants (1%<MAF<5%) with platelet count (PLT), red cell indices (MCH, MCV) and high-density lipoprotein (HDL) cholesterol. Applying fine-mapping analysis to 233 known and novel loci associated with the twenty traits, we resolve associations of 59 loci to credible sets of 20 or less variants, and describe trait enrichments within regions of predicted regulatory function. These findings augment understanding of the allelic architecture of risk factors for cardiometabolic and hematologic diseases, and provide additional functional insights with the identification of potentially novel biological targets.