McQueen Matthew B, Bertram Lars, Rimm Eric B, Blacker Deborah, Santangelo Susan L
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S96. doi: 10.1186/1471-2156-4-S1-S96.
Because high blood pressure, altered lipid levels, obesity, and diabetes so frequently occur together, they are sometimes collectively referred to as the metabolic syndrome. While there have been many studies of each metabolic syndrome trait separately, few studies have attempted to analyze them combined, i.e., as one composite variable, in quantitative trait linkage or association analysis. We used genotype and phenotype data from the Framingham Heart Study to perform a full-genome scan for quantitative trait loci underlying the metabolic syndrome.
Heritability estimates for all of the covariate-adjusted and age- and gender-standardized individual traits, and the composite metabolic syndrome trait, were all fairly high (0.39-0.62), and the composite trait was among the highest at 0.61. The composite trait yielded no regions with suggestive linkage by Lander and Kruglyak's criteria, although there were several noteworthy regions for individual traits, some of which were also observed for the composite variable.
Despite its high heritability, the composite metabolic syndrome trait variable did not increase the power to detect or localize linkage peaks in this sample. However, this strategy and related methods of combining correlated individual traits deserve further investigation, particularly in settings with complex causal pathways.
由于高血压、血脂异常、肥胖和糖尿病经常同时出现，它们有时被统称为代谢综合征。虽然已经有许多针对每种代谢综合征特征的单独研究，但很少有研究尝试在数量性状连锁或关联分析中将它们作为一个复合变量进行综合分析。我们使用弗雷明汉心脏研究的基因型和表型数据，对代谢综合征潜在的数量性状位点进行全基因组扫描。
所有经协变量调整以及年龄和性别标准化的个体特征，以及复合代谢综合征特征的遗传力估计值都相当高（0.39 - 0.62），复合特征的遗传力估计值最高，为0.61。根据兰德和克鲁格利亚克的标准，复合特征未产生具有提示性连锁的区域，尽管个体特征有几个值得注意的区域，其中一些在复合变量中也有观察到。
尽管复合代谢综合征特征变量具有较高的遗传力，但在该样本中它并未提高检测或定位连锁峰的能力。然而，这种将相关个体特征进行组合的策略及相关方法值得进一步研究，尤其是在具有复杂因果途径的情况下。
