North Kari E, Martin Lisa J, Dyer Tom, Comuzzie Anthony G, Williams Jeff T
Department of Epidemiology, University of North Carolina, Chapel Hill 27514 USA.
BMC Genet. 2003 Dec 31;4 Suppl 1(Suppl 1):S98. doi: 10.1186/1471-2156-4-S1-S98.
Despite strong evidence for a genetic component to variation in high-density lipoprotein cholesterol levels (HDL-C), specific polymorphisms associated with normal variation in HDL-C have not been identified. It is known, however, that HDL-C levels are influenced in complex ways by factors related to age and sex. In this paper, we examined the evidence for age- and sex-specific linkage of HDL-C in a longitudinal sample of participants from the Framingham Heart Study. To determine if aging could influence our ability to detect linkage, we explored the evidence for linkage of HDL-C at three time points, t1, t2, and t3, spaced approximately 8 years apart and corresponding respectively to visits 11, 15, and 20 for the original cohort and 1, 2, and 4 for the offspring and spouses. Additionally, to examine the effects of sex on linkage at each time point, we estimated the heritability and genetic correlation of HDL-C, performed linkage analysis of HDL-C, tested for genotype-by-sex interaction at a QTL, and performed linkage analysis of HDL-C in males and females separately.
In women, we found evidence for a QTL on chromosome 2q influencing HDL-C variation. Although the QTL could be detected in the combined sample of males and females at the first time point, the linkage was not significant at subsequent time points.
尽管有充分证据表明高密度脂蛋白胆固醇水平（HDL-C）的变异存在遗传成分，但尚未确定与HDL-C正常变异相关的特定多态性。然而，已知HDL-C水平受到与年龄和性别相关因素的复杂影响。在本文中，我们在弗雷明汉心脏研究参与者的纵向样本中研究了HDL-C的年龄和性别特异性连锁证据。为了确定衰老是否会影响我们检测连锁的能力，我们在三个时间点（t1、t2和t3）探索了HDL-C的连锁证据，这三个时间点相隔约8年，分别对应于原始队列的第11、15和20次访视以及后代和配偶的第1、2和4次访视。此外，为了研究性别对每个时间点连锁的影响，我们估计了HDL-C的遗传力和遗传相关性，进行了HDL-C的连锁分析，在一个数量性状基因座（QTL）上测试了基因型与性别的相互作用，并分别对男性和女性进行了HDL-C的连锁分析。
在女性中，我们发现2号染色体q臂上存在一个影响HDL-C变异的QTL的证据。尽管在第一个时间点的男性和女性合并样本中可以检测到该QTL，但在随后的时间点连锁并不显著。
