Horne Benjamin D, Malhotra Alka, Camp Nicola J
Genetic Epidemiology, Department of Medical Informatics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S93. doi: 10.1186/1471-2156-4-S1-S93.
High triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) jointly increase coronary disease risk. We performed linkage analysis for TG/HDL-C ratio in the Framingham Heart Study data as a quantitative trait, using methods implemented in LINKAGE, GENEHUNTER (GH), MCLINK, and SOLAR. Results were compared to each other and to those from a previous evaluation using SOLAR for TG/HDL-C ratio on this sample. We also investigated linked pedigrees in each region using by-pedigree analysis.
Fourteen regions with at least suggestive linkage evidence were identified, including some that may increase and some that may decrease coronary risk. Ten of the 14 regions were identified by more than one analysis, and several of these regions were not previously detected. The best regions identified for each method were on chromosomes 2 (LOD = 2.29, MCLINK), 5 (LOD = 2.65, GH), 7 (LOD = 2.67, SOLAR), and 22 (LOD = 3.37, LINKAGE). By-pedigree multi-point LOD values in MCLINK showed linked pedigrees for all five regions, ranging from 3 linked pedigrees (chromosome 5) to 14 linked pedigrees (chromosome 7), and suggested localizations of between 9 cM and 27 cM in size.
Reasonable concordance was found across analysis methods. No single method identified all regions, either by full sample LOD or with by-pedigree analysis. Concordance across methods appeared better at the pedigree level, with many regions showing by-pedigree support in MCLINK when no evidence was observed in the full sample. Thus, investigating by-pedigree linkage evidence may provide a useful tool for evaluating linkage regions.
高甘油三酯（TG）和低高密度脂蛋白胆固醇（HDL-C）共同增加冠心病风险。我们在弗雷明汉心脏研究数据中对TG/HDL-C比值作为定量性状进行连锁分析，使用LINKAGE、GENEHUNTER（GH）、MCLINK和SOLAR中实现的方法。将结果相互比较，并与之前使用SOLAR对该样本的TG/HDL-C比值进行评估的结果进行比较。我们还使用逐系谱分析研究了每个区域中的连锁家系。
确定了14个至少有提示性连锁证据的区域，包括一些可能增加和一些可能降低冠心病风险的区域。14个区域中的10个通过不止一种分析方法被识别出来，其中几个区域以前未被检测到。每种方法确定的最佳区域位于2号染色体（LOD = 2.29，MCLINK）、5号染色体（LOD = 2.65，GH）、7号染色体（LOD = 2.67，SOLAR）和22号染色体（LOD = 3.37，LINKAGE）上。MCLINK中的逐系谱多点LOD值显示所有五个区域均有连锁家系，范围从3个连锁家系（5号染色体）到14个连锁家系（7号染色体），并提示定位大小在9厘摩至27厘摩之间。
在各种分析方法之间发现了合理的一致性。没有一种单一方法通过全样本LOD或逐系谱分析识别出所有区域。方法之间的一致性在系谱水平上似乎更好，当在全样本中未观察到证据时，许多区域在MCLINK中显示出逐系谱支持。因此，研究逐系谱连锁证据可能为评估连锁区域提供一个有用的工具。
