国际全基因组关联研究联盟确定了与儿童和青少年血压相关的新基因座。
International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.
作者信息
Parmar Priyakumari Ganesh, Taal H Rob, Timpson Nicholas J, Thiering Elisabeth, Lehtimäki Terho, Marinelli Marcella, Lind Penelope A, Howe Laura D, Verwoert Germaine, Aalto Ville, Uitterlinden Andre G, Briollais Laurent, Evans Dave M, Wright Margie J, Newnham John P, Whitfield John B, Lyytikäinen Leo-Pekka, Rivadeneira Fernando, Boomsma Dorrett I, Viikari Jorma, Gillman Matthew W, St Pourcain Beate, Hottenga Jouke-Jan, Montgomery Grant W, Hofman Albert, Kähönen Mika, Martin Nicholas G, Tobin Martin D, Raitakari Ollie, Vioque Jesus, Jaddoe Vincent W V, Jarvelin Marjo-Riita, Beilin Lawrence J, Heinrich Joachim, van Duijn Cornelia M, Pennell Craig E, Lawlor Debbie A, Palmer Lyle J
出版信息
Circ Cardiovasc Genet. 2016 Jun;9(3):266-278. doi: 10.1161/CIRCGENETICS.115.001190. Epub 2016 Mar 11.
BACKGROUND
Our aim was to identify genetic variants associated with blood pressure (BP) in childhood and adolescence.
METHODS AND RESULTS
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.
CONCLUSIONS
Our results suggest that genetic determinants of BP act from childhood, develop over the lifecourse, and show some evidence of age-specific effects.
背景
我们的目标是识别与儿童期和青少年期血压（BP）相关的基因变异。
方法与结果
对早期遗传学与生命历程流行病学（EAGLE）联盟中参与研究的欧洲血统队列的全基因组关联研究数据进行了三个阶段的荟萃分析；青春期前（4 - 7岁）、青春期（8 - 12岁）和青春期后（13 - 20岁）。在特定年龄阶段，两个新的基因座被确定与收缩压存在全基因组关联：青春期前的rs1563894（ITGA11，位于活性H3K27Ac标记以及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）以及青春期的rs872256（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<5×10⁻³的P值阈值，我们发现在我们的研究中不同年龄阶段的变异之间以及三个阶段中任何一个阶段的几个单核苷酸多态性与成人血压相关单核苷酸多态性之间存在一些重叠。
结论
我们的结果表明，血压的遗传决定因素从儿童期就开始起作用，在生命历程中发展，并显示出一些年龄特异性效应的证据。
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