Comparison of heritability of Cystatin C- and creatinine-based estimates of kidney function and their relation to heritability of cardiovascular disease.
Comparison of heritability of Cystatin C- and creatinine-based estimates of kidney function and their relation to heritability of cardiovascular disease.
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DOI：
10.1161/jaha.114.001467
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发表时间：
2015-01-14
影响因子：
5.4
通讯作者：
Svensson P
中科院分区：
文献类型：
--
作者：
Arpegård J;Viktorin A;Chang Z;de Faire U;Magnusson PK;Svensson P
肾功能下降是心血管疾病（CVD）的既定风险因素。肾功能和心血管疾病的估计之间的因果机制是复杂的，这些表型的变异性的遗传和环境因素的相对重要性的调查可以提供新的知识。对12313对双生子血清胱抑素C和肌酐水平进行分析。通过结构方程模型和全基因组复杂性状分析（GCTA）估计这些性状和CVD的单变量和双变量遗传力，以独立确认加性遗传效应。双生子模型估计的胱抑素C遗传度在男性中为0.55（95%置信区间[CI]，0.49 - 0.60），在女性中为0.63（0.59 - 0.66），在两种性别中合并为0.60（0.56 - 0.63）。对于肌酐，遗传力估计值在相同范围内。男性心血管疾病的遗传度为0.39（0.02至0.67），女性为0.20（0.00至0.61）。Cystatin C与CVD相关性之间的表型相关性在男性中为0.16（0.12至0.20），在女性中为0.17（0.13至0.21），而男性中的遗传相关性为0.41（0.21至0.62），而女性中无显著性。GCTA谷值时，Cystatin C和肌酐的遗传度在两种性别中分别估计为0.40（SE 0.07，P= 8 E −9）和0.19（SE 0.07，P=0.003）。与既往研究相比，基于双胞胎模型的Cystatin C遗传率较高。Cystatin C和CVD在男性中的共变异部分由加性遗传成分解释，表明Cystatin C和CVD共享遗传影响。GCTA为Cystatin C的加性遗传效应对性状变异的显著贡献提供了独立的证据。
Decreased renal function is an established risk factor for cardiovascular disease (CVD). Causal mechanisms between estimates of renal function and CVD are intricate and investigation of the relative importance of genetic and environmental factors for the variability of these phenotypes could provide new knowledge. Cystatin C and creatinine levels in 12 313 twins were analyzed. Uni‐ and bivariate heritability for these traits and CVD was estimated through structured equation modelling and genome‐wide complex trait analysis (GCTA) in order to independently confirm additive genetic effects. Twin model‐estimated heritability of Cystatin C was 0.55 (95% confidence interval [CI], 0.49 to 0.60) in men, 0.63 (0.59 to 0.66) in women, and 0.60 (0.56 to 0.63) in both sexes combined. For creatinine, heritability estimates were in the same range. Heritability of CVD was 0.39 (0.02 to 0.67) in men and 0.20 (0.00 to 0.61) in women. The phenotypic correlation between Cystatin C and CVD correlation was 0.16 (0.12 to 0.20) in men and 0.17 (0.13 to 0.21) in women, whereas the genetic correlation in males was 0.41 (0.21 to 0.62) while it was non‐significant in females. Trough GCTA, the heritability of Cystatin C and creatinine in both sexes combined was estimated to 0.40 (SE 0.07, P=8E−9) and 0.19 (SE 0.07, P=0.003), respectively. Twin model‐based heritability of Cystatin C was higher compared to previous studies. Co‐variation between Cystatin C and CVD in males was partly explained by additive genetic components, indicating that Cystatin C and CVD share genetic influences. The GCTA provided independent evidence for significant contribution of additive genetics to trait variance of Cystatin C.