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遗传因素对冠心病死亡的影响及已知危险因素的作用:两种脆弱模型的比较

Genetic influences on CHD-death and the impact of known risk factors: comparison of two frailty models.

作者信息

Zdravkovic Slobodan, Wienke Andreas, Pedersen Nancy L, Marenberg Marjorie E, Yashin Anatoli I, de Faire Ulf

机构信息

Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

出版信息

Behav Genet. 2004 Nov;34(6):585-92. doi: 10.1007/s10519-004-5586-1.

Abstract

The importance of some recognized risk factors on genetic influences for coronary heart disease (CHD) needs further clarification. The aim of the present study was therefore to study the impact of known risk factors on genetic influences for CHD-death. Both twin (correlated gamma-frailty) and non-twin models (univariate gamma-frailty) were utilized and compared regarding their suitability for genetic analyses. The study population consisted of twins born in Sweden between 1886 and 1925. As expected, our findings indicate that genetic influences are important for CHD-death. Inclusion of risk factors in the twin-model increased heritability estimates, primarily due to a substantial reduction in non-shared environmental variances. The genetic influences for CHD-death are only marginally mediated through the risk factors among males, but more so among females. Although the outcome phenotype used in the present study is not behavioral, the analyses demonstrate the potential of frailty models for quantitative genetic analyses of categorical phenotypes.

摘要

一些已公认的冠心病(CHD)遗传影响风险因素的重要性需要进一步阐明。因此,本研究的目的是探讨已知风险因素对冠心病死亡遗传影响的作用。采用了双生子模型(相关γ-脆弱性模型)和非双生子模型(单变量γ-脆弱性模型),并比较了它们在遗传分析中的适用性。研究人群包括1886年至1925年间在瑞典出生的双胞胎。正如预期的那样,我们的研究结果表明遗传影响对冠心病死亡很重要。在双生子模型中纳入风险因素提高了遗传度估计值,主要是由于非共享环境方差大幅降低。冠心病死亡的遗传影响在男性中仅通过风险因素有轻微介导作用,而在女性中则更为明显。尽管本研究中使用的结局表型不是行为表型,但分析证明了脆弱性模型在分类表型定量遗传分析中的潜力。

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