A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.
A blood pressure genetic risk score is a significant predictor of incident cardiovascular events in 32,669 individuals.
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DOI：
10.1161/hypertensionaha.111.00649
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发表时间：
2013-05
期刊：
影响因子：
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通讯作者：
Newton-Cheh C
中科院分区：
文献类型：
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作者：
Havulinna AS;Kettunen J;Ukkola O;Osmond C;Eriksson JG;Kesäniemi YA;Jula A;Peltonen L;Kontula K;Salomaa V;Newton-Cheh C
最近的全基因组关联研究（GWASs）已经确定了与血压（BP）相关的遗传变异。我们研究了由这些变异构建的遗传风险评分（GRSs）是否能预测心血管疾病（CVD）事件的发生。我们在几个芬兰队列中对32个常见的单核苷酸多态性（snp）进行了基因分型，在排除了流行的心血管疾病病例后，共有32,669个个体。中位随访时间为9.8年，期间发生了2295例CVD事件。我们分别为收缩压（SBP）和舒张压（DBP）创建了GRSs，方法是将每个SNP的风险等位基因计数乘以已发表的GWASs中估计的效应大小。在每个队列中，我们对包括基线血压在内的临床因素进行了Cox回归分析。结果通过反向方差加权固定效应荟萃分析合并。GRSs与收缩压、舒张压和基线高血压密切相关（均p<10−62）。在调整年龄、年龄平方和性别后，收缩压和舒张压遗传风险评分最高五分位数与最低五分位数的风险比分别为1.25 （1.07-1.46,p = 0.006）和1.23 (1.05-1.43,p = 0.01)；1.24 （1.01-1.53, p = 0.04）和1.35 (1.09-1.66,p = 0.005)；复合CVD为1.23 （1.08-1.40,p = 2×10−6）和1.26 （1.11-1.44,p = 5×10−4）。总之，GWASs的BP发现得到了强烈的复制。由真正的BP snp组成的GRSs预测心血管疾病的风险，与这些变异对BP的终身影响一致。
Recent genome-wide association studies (GWASs) have identified genetic variants associated with blood pressure (BP). We investigated whether genetic risk scores (GRSs) constructed of these variants would predict incident cardiovascular disease (CVD) events. We genotyped 32 common single nucleotide polymorphisms (SNPs) in several Finnish cohorts, with up to 32,669 individuals after exclusion of prevalent CVD cases. The median follow-up was 9.8 years, during which 2,295 incident CVD events occurred. We created GRSs separately for systolic (SBP) and diastolic BP (DBP) by multiplying the risk allele count of each SNP by the effect size estimated in published GWASs. We performed Cox regression analyses with and without adjustment for clinical factors including BP at baseline in each cohort. The results were combined by inverse variance-weighted fixed-effects meta-analysis. The GRSs were strongly associated with SBP and DBP and baseline hypertension (all p<10−62). Hazard ratios comparing the highest quintiles of SBP and DBP genetic risk scores with the lowest quintiles after adjustment for age, age squared and sex, were 1.25 (1.07–1.46, p = 0.006) and 1.23 (1.05–1.43, p = 0.01), respectively, for incident coronary heart disease; 1.24 (1.01–1.53, p = 0.04) and 1.35 (1.09–1.66, p = 0.005) for incident stroke; and 1.23 (1.08–1.40, p = 2×10−6) and 1.26 (1.11–1.44, p = 5×10−4) for composite CVD. In conclusion, BP findings from GWASs are strongly replicated. GRSs comprised of bona fide BP SNPs predicted cardiovascular disease risk, consistent with a life-long effect on BP of these variants collectively.