International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.
International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.
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国际基因组协会研究联盟确定了与儿童和青少年血压相关的新基因座。
DOI：
10.1161/circgenetics.115.001190
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发表时间：
2016-06
期刊：
影响因子：
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通讯作者：
Early Genetics and Lifecourse Epidemiology Consortium
中科院分区：
文献类型：
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作者：
Parmar PG;Taal HR;Timpson NJ;Thiering E;Lehtimäki T;Marinelli M;Lind PA;Howe LD;Verwoert G;Aalto V;Uitterlinden AG;Briollais L;Evans DM;Wright MJ;Newnham JP;Whitfield JB;Lyytikäinen LP;Rivadeneira F;Boomsma DI;Viikari J;Gillman MW;St Pourcain B;Hottenga JJ;Montgomery GW;Hofman A;Kähönen M;Martin NG;Tobin MD;Raitakari O;Vioque J;Jaddoe VWV;Jarvelin MR;Beilin LJ;Heinrich J;van Duijn CM;Pennell CE;Lawlor DA;Palmer LJ;Early Genetics and Lifecourse Epidemiology Consortium
我们的目的是确定与儿童和青少年血压（BP）相关的遗传变异。对来自早期遗传学和生命过程流行病学（EAGLE）联盟的参与欧洲血统队列的全基因组关联研究数据进行了3个时期的荟萃分析;青春期前（4-7岁），青春期（8-12岁）和青春期后（13-20岁）。两个新的基因座被确定为在特定年龄段与收缩压有全基因组关联：青春期前rs 1563894（ITGA 11，位于活性H3 K27 Ac标记和转录因子染色质免疫沉淀和5′-C-磷酸-G-3′甲基化位点）（P=2.86×10-8）和青春期rs 872256（P=8.67×10-9）。几个单核苷酸多态性簇也与儿童期血压相关（P<5×10-3）。使用P值阈值<5×10-3，我们发现在我们研究中不同年龄阶段的变异中，以及在3个年龄阶段中的任何一个中的几个单核苷酸多态性与成人BP相关单核苷酸多态性之间存在一些重叠。我们的研究结果表明，BP的遗传决定因素从童年起作用，在整个生命过程中发展，并显示出一些年龄特异性影响的证据。
Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence. Genome-wide association study data from participating European ancestry cohorts of the Early Genetics and Lifecourse Epidemiology (EAGLE) Consortium was meta-analyzed across 3 epochs; prepuberty (4–7 years), puberty (8–12 years), and postpuberty (13–20 years). Two novel loci were identified as having genome-wide associations with systolic BP across specific age epochs: rs1563894 (ITGA11, located in active H3K27Ac mark and transcription factor chromatin immunoprecipitation and 5′-C-phosphate-G-3′ methylation site) during prepuberty (P=2.86×10–8) and rs872256 during puberty (P=8.67×10–9). Several single-nucleotide polymorphism clusters were also associated with childhood BP at P<5×10–3. Using a P value threshold of <5×10–3, we found some overlap in variants across the different age epochs within our study and between several single-nucleotide polymorphisms in any of the 3 epochs and adult BP-related single-nucleotide polymorphisms. Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.