Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.
Evidence for bivariate linkage of obesity and HDL-C levels in the Framingham Heart Study.
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DOI：
10.1186/1471-2156-4-s1-s52
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发表时间：
2003-12-31
期刊：
影响因子：
2.9
通讯作者：
Framingham Heart Study
中科院分区：
文献类型：
--
作者：
Arya R;Lehman D;Hunt KJ;Schneider J;Almasy L;Blangero J;Stern MP;Duggirala R;Framingham Heart Study
流行病学研究表明，肥胖和低高密度脂蛋白（HDL）水平是强烈的心血管危险因素，并且这些特征呈负相关。尽管人们相信这些性状在一定程度上是由于多效性而相关的，但对通常影响肥胖和血脂异常的特定基因的了解非常有限。为了解决这个问题，我们首先使用与分布在 330 个谱系的 1702 名受试者相关的弗雷明汉心脏研究数据，对体重指数 (BMI) 和 HDL-C 进行单变量多点连锁分析，以确定影响这些表型变异的基因座。随后，我们进行了双变量多点连锁分析，以检测影响这两个性状之间共变的共同基因座。我们扫描了基因组，并使用程序 SOLAR 识别了标记 D6S1009 附近影响 BMI 变化 (LOD = 3.9) 的主要基因座。我们还确定了靠近 2 号染色体上标记 D2S1334 的 HDL-C 主要基因座（LOD = 3.5）和靠近 6 号染色体上标记 D6S1009 的另一个区域，并具有连锁证据（LOD = 2.7）。由于这两种表型已独立映射到 6q 染色体上的同一区域，因此我们使用 SOLAR 的双变量多点连锁方法。 BMI 和 HDL-C 的双变量连锁分析表明，标记 D6S1009 附近的遗传区域含有通常影响这些表型的主要基因（双变量 LOD = 6.2；LODeq = 5.5），并且似乎提高了将相关性状精确映射到区域的能力。我们发现了具有多效性的数量性状基因座的大量证据，该基因座似乎影响弗雷明汉数据中的 BMI 和 HDL-C 表型。
Epidemiological studies have indicated that obesity and low high-density lipoprotein (HDL) levels are strong cardiovascular risk factors, and that these traits are inversely correlated. Despite the belief that these traits are correlated in part due to pleiotropy, knowledge on specific genes commonly affecting obesity and dyslipidemia is very limited. To address this issue, we first conducted univariate multipoint linkage analysis for body mass index (BMI) and HDL-C to identify loci influencing variation in these phenotypes using Framingham Heart Study data relating to 1702 subjects distributed across 330 pedigrees. Subsequently, we performed bivariate multipoint linkage analysis to detect common loci influencing covariation between these two traits. We scanned the genome and identified a major locus near marker D6S1009 influencing variation in BMI (LOD = 3.9) using the program SOLAR. We also identified a major locus for HDL-C near marker D2S1334 on chromosome 2 (LOD = 3.5) and another region near marker D6S1009 on chromosome 6 with suggestive evidence for linkage (LOD = 2.7). Since these two phenotypes have been independently mapped to the same region on chromosome 6q, we used the bivariate multipoint linkage approach using SOLAR. The bivariate linkage analysis of BMI and HDL-C implicated the genetic region near marker D6S1009 as harboring a major gene commonly influencing these phenotypes (bivariate LOD = 6.2; LODeq = 5.5) and appears to improve power to map the correlated traits to a region, precisely. We found substantial evidence for a quantitative trait locus with pleiotropic effects, which appears to influence both BMI and HDL-C phenotypes in the Framingham data.