Cox Hannah C, Bellis Claire, Lea Rod A, Quinlan Sharon, Hughes Roger, Dyer Thomas, Charlesworth Jac, Blangero John, Griffiths Lyn R
Genomics Research Centre, Griffith Institute for Health and Medical Research, Griffith University, Gold Coast, Qld., Australia.
Hum Hered. 2009;68(1):55-64. doi: 10.1159/000210449. Epub 2009 Apr 1.
OBJECTIVE(S): An individual's risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island.
This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis.
A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h(2) = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h(2) = 0.33) and 4 (h(2) = 0.42), respectively.
CONCLUSION(S): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.
个体患心血管疾病（CVD）的风险受遗传因素影响。本研究聚焦于在源自诺福克岛的独特人群隔离群体中绘制CVD风险性状的基因座图谱。
本调查针对377名源自该群体创始人的个体。主成分分析用于从11种心血管风险性状中提取正交成分。多点方差成分法用于使用SOLAR评估全基因组与导出因子的连锁关系。377名相关个体中的285名对连锁分析具有信息价值。
共得出4个主成分，占总方差的83%。主成分1加载有身体大小指标；主成分2加载有身体大小、胆固醇和甘油三酯水平；主成分3加载有血压；主成分4加载有低密度脂蛋白胆固醇和总胆固醇水平。在5号染色体q35区域观察到主成分2（h(2) = 0.35）存在连锁的提示性证据（LOD = 1.85；p = 0.0008）。而在10号染色体p11.2（LOD = 1.27；p = 0.005）和12号染色体q13（LOD = 1.63；p = 0.003）的峰值区域分别观察到与主成分1（h(2) = 0.33）和4（h(2) = 0.42）共分离。
本研究在一个独特的隔离群体中调查了多种CVD风险性状。研究结果支持CVD风险性状的聚类，并为5号染色体q35上一个与体重、腰围、高密度脂蛋白胆固醇和总甘油三酯水平共分离的区域提供了有趣的证据。
