Howe Laura D, Parmar Priyakumari G, Paternoster Lavinia, Warrington Nicole M, Kemp John P, Briollais Laurent, Newnham John P, Timpson Nicholas J, Smith George Davey, Ring Susan M, Evans David M, Tilling Kate, Pennell Craig E, Beilin Lawrie J, Palmer Lyle J, Lawlor Debbie A
MRC Integrative Epidemiology Unit at the University of Bristol.
Circ Cardiovasc Genet. 2013 Dec;6(6):608-14. doi: 10.1161/CIRCGENETICS.113.000197. Epub 2013 Nov 7.
Blood pressure (BP) tends to increase across childhood and adolescence, but the genetic influences on rates of BP change are not known. Potentially important genetic influences could include genetic variants identified in genome-wide association studies of adults as being associated with BP, height, and body mass index. Understanding the contribution of these genetic variants to changes in BP across childhood and adolescence could yield understanding into the life course development of cardiovascular risk.
Pooling data from 2 cohorts (the Avon Longitudinal Study of Parents and Children [n=7013] and the Western Australian Pregnancy Cohort [n=1459]), we examined the associations of allelic scores of 29 single-nucleotide polymorphisms (SNPs) for adult BP, 180 height SNPs, and 32 body mass index SNPs, with trajectories of systolic BP (SBP) from 6 to 17 years of age, using linear spline multilevel models. The allelic scores of BP and body mass index SNPs were associated with SBP at 6 years of age (per-allele effect sizes, 0.097 mm Hg [SE, 0.039 mm Hg] and 0.107 mm Hg [SE, 0.037 mm Hg]); associations with age-related changes in SBP between 6 and 17 years of age were of small magnitude and imprecisely estimated. The allelic score of height SNPs was only weakly associated with SBP changes. No sex or cohort differences in genetic effects were observed.
Allelic scores of BP and body mass index SNPs demonstrated associations with SBP at 6 years of age with a similar magnitude but were not strongly associated with changes in SBP with age between 6 and 17 years. Further work is required to identify variants associated with changes with age in BP.
血压(BP)在儿童期和青少年期往往会升高,但基因对血压变化率的影响尚不清楚。潜在的重要基因影响可能包括在成人全基因组关联研究中确定的与血压、身高和体重指数相关的基因变异。了解这些基因变异对儿童期和青少年期血压变化的贡献,可能有助于深入了解心血管风险的生命历程发展。
汇总来自2个队列(阿冯父母与儿童纵向研究[n = 7013]和西澳大利亚妊娠队列[n = 1459])的数据,我们使用线性样条多级模型,研究了29个成人血压单核苷酸多态性(SNP)、180个身高SNP和32个体重指数SNP的等位基因分数与6至17岁收缩压(SBP)轨迹的关联。血压和体重指数SNP的等位基因分数与6岁时的SBP相关(每个等位基因的效应大小分别为0.097 mmHg [标准误,0.039 mmHg]和0.107 mmHg [标准误,0.037 mmHg]);与6至l7岁SBP的年龄相关变化的关联程度较小且估计不准确。身高SNP的等位基因分数与SBP变化的关联较弱。未观察到基因效应的性别或队列差异。
血压和体重指数SNP的等位基因分数在6岁时与SBP的关联程度相似,但与6至17岁SBP随年龄的变化没有强烈关联。需要进一步开展工作以确定与血压随年龄变化相关的变异。