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. 2003 Dec 31;4 Suppl 1(Suppl 1):S24.
doi: 10.1186/1471-2156-4-S1-S24.

Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures

Shaoqi Rao  1 , Lin Li, Xia Li, Kathy L Moser, Zheng Guo, Gongqing Shen, Ruth Cannata, Erich Zirzow, Eric J Topol, Qing Wang
Affiliations

Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures

Shaoqi Rao et al. BMC Genet. .

Abstract

Background: Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension phenotypes as well as epidemiological risk factors, respectively. Direct modelling of a large number of serially and biologically correlated traits in the context of linkage analysis can be prohibitively complex. Alternatively, we may consider using univariate transformation for linkage analysis of longitudinal repeated measures.

Results: We evaluated the utility of three conventional summary measures (mean, slope, and principal components) for genetic linkage analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the Framingham Heart Study. Except for the temporal slope, all of the summary methods and the multivariate analysis identified the previously reported region, marker GATA64A09, for systolic blood pressure or high blood pressure. Further analysis revealed that this region may harbor gene(s) affecting human blood pressure at multiple stages of life.

Conclusion: We conclude that mean and principal components are feasible alternatives for genetic linkage analysis of longitudinal phenotypes, but the slope might have a separate genetic basis from that of the original longitudinal phenotypes.

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Figures

Figure 1
Figure 1
Linkage profiles for two longitudinal summary measures Lines depict the -log10 (P-value) along chromosome 10. The dashed line indicates the arithmetic mean and the solid line indicates the temporal slope of longitudinal systolic blood pressures. The results were obtained by new Haseman-Elston regression using SAGE package.
Figure 2
Figure 2
Cumulative t2 statistics for five principal components (PRIN1-PRIN5) of two longitudinal phenotypes Each line depicts the sum of t2 values (for t > 0) for all of principal components up to and including the ith for systolic blood pressure (a) and hypertension (b).
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