Diego Vincent P, Atwood Larry, Mathias Rasika A, Almasy Laura
Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, Texas 78245, USA.
Genet Epidemiol. 2003;25 Suppl 1:S29-35. doi: 10.1002/gepi.10281.
This paper examines the consistency of genetic analyses across time, both in the context of replicating results from one data collection point to the next, and from the perspective of modeling longitudinal processes. This summary originates from the examination of findings from nine papers from Genetic Analysis Workshop (GAW) 13 that reported on analyses of longitudinal data of a variety of traits from the Framingham Heart Study. These analyses include both assessments of consistency of aggregate genetic effects, in the form of estimation of heritability and relative risk of disease, as well as localization of quantitative trait loci (QTLs) by genome-wide linkage screens. Consistency varied widely by trait, possibly reflecting differences in measurement error, secular trends, or underlying biological features such as genotype x age interaction. Quantitatively, comparing magnitudes of estimates across age or time, heritability estimates showed greater consistency than LOD scores. However, qualitatively, the same regions of interest were often identified in genome scans from different time points or different ages. Estimates of sibling recurrence risk, on the other hand, showed little consistency. Heritabilities were greater when participants were matched by age than when they were matched by date of examination. Multivariate approaches, either in use of multiple traits or in use of multiple measures of the same trait, appeared to provide stronger genetic signals both for relative risk and for linkage. Finally, modeling of longitudinal processes provided evidence for genotype x age interactions that may partially explain variation in results of genetic analyses across time or age.
本文考察了基因分析在时间维度上的一致性，这既体现在将一个数据收集点的结果复制到下一个数据收集点的背景下，也体现在对纵向过程进行建模的视角下。本综述源于对遗传分析研讨会（GAW）13的九篇论文研究结果的考察，这些论文报告了对弗雷明汉心脏研究中各种性状的纵向数据的分析。这些分析既包括以遗传力估计和疾病相对风险形式对总体遗传效应一致性的评估，也包括通过全基因组连锁筛选对数量性状位点（QTL）的定位。一致性因性状不同而有很大差异，这可能反映了测量误差、长期趋势或潜在生物学特征（如基因型×年龄相互作用）的差异。从数量上看，比较不同年龄或时间的估计值大小，遗传力估计值比LOD分数显示出更高的一致性。然而，从质量上看，在来自不同时间点或不同年龄的基因组扫描中，常常会识别出相同的感兴趣区域。另一方面，同胞复发风险估计值显示出的一致性很小。当参与者按年龄匹配时的遗传力比按检查日期匹配时更高。多变量方法，无论是使用多个性状还是使用同一性状的多个测量指标，似乎都能为相对风险和连锁提供更强的遗传信号。最后，对纵向过程的建模为基因型×年龄相互作用提供了证据，这可能部分解释了基因分析结果在时间或年龄上的差异。
