Shi Gang, Gu Chi C, Kraja Aldi T, Arnett Donna K, Myers Richard H, Pankow James S, Hunt Steven C, Rao Dabeeru C
Division of Biostatistics, Washington University School of Medicine, Campus Box 8067, 660 S Euclid Ave, St. Louis, MO 63110-1093, USA.
Hypertension. 2009 Jan;53(1):35-41. doi: 10.1161/HYPERTENSIONAHA.108.120071. Epub 2008 Nov 24.
Genome-wide linkage analysis was performed for systolic and diastolic blood pressures in the Hypertension Genetic Epidemiology Network. We investigated the role of gene-age interactions using a recently developed variance components method that incorporates age variation in genetic effects. Substantially improved linkage evidence, in terms of both the number of linkage peaks and their significance levels, was observed. Twenty-six linkage peaks were identified with maximum logarithm of odds scores ranging between 3.0 and 4.6, 15 of which were cross-validated by the literature. The chromosomal region 1p36 that showed the highest logarithm of odds score in our study was found to be supported by evidence from 3 studies. The new method also led to vastly improved validation across ethnic groups. Ten of the 15 supported linkage peaks were cross-validated between 2 different ethnic groups, and 2 peaks on chromosomal region 1q31 and 16p11 were validated in 3 ethnic groups. In conclusion, this investigation demonstrates that genetic effects on blood pressure vary by age. The improved genetic linkage results presented here should help to identify the specific genetic variants that explain the observed results.
高血压遗传流行病学网络对收缩压和舒张压进行了全基因组连锁分析。我们使用一种最近开发的纳入了遗传效应年龄变异的方差成分法,研究了基因-年龄相互作用的作用。在连锁峰数量及其显著性水平方面,均观察到连锁证据有显著改善。共识别出26个连锁峰,最大对数优势分数在3.0至4.6之间,其中15个通过文献交叉验证。在我们的研究中显示出最高对数优势分数的染色体区域1p36,有3项研究的证据支持。新方法还极大地改善了不同种族群体间的验证。15个得到支持的连锁峰中有10个在两个不同种族群体间进行了交叉验证,染色体区域1q31和16p11上的2个峰在3个种族群体中得到验证。总之,本研究表明基因对血压的影响随年龄而变化。这里呈现的改进后的遗传连锁结果应有助于识别解释观察结果的特定遗传变异。