Feitosa Mary E, Rice Treva, Borecki Ingrid B, Rankinen Tuomo, Leon Arthur S, Skinner James S, Després Jean-Pierre, Blangero John, Bouchard Claude, Rao D C
Division of Statistical Genomics in the Center for Genome Sciences, Washington University School of Medicine, Saint Louis, MO, USA.
Hum Biol. 2006 Jun;78(3):317-27. doi: 10.1353/hub.2006.0043.
To determine whether a common quantitative trait locus (QTL) influences the variation of fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels, we used a bivariate multipoint linkage analysis with 654 polymorphic markers in 99 white and 101 black families. The phenotypes were investigated under two conditions: at baseline and after a 20-week exercise training intervention. A maximum genome-wide bivariate LOD score of 3.0 (p = 0.00010) was found on chromosome 12q23-q24, located within the IGF1 gene (insulin-like growth factor 1, at 107 cM) for TG and HDL-C at baseline in whites. This bivariate linkage peak is considerably higher than the univariate linkage results at the same chromosome location for either trait (for TG, LOD = 2.07, p = 0.00108; for HDL-C, LOD = 2.04, p = 0.00101). The genetic correlations between baseline TG and HDL-C levels were -0.14 for the residual and -0.33 for the QTL components. Moreover, association analysis showed that TG, HDL-C, and IGF1 are significantly associated (p = 0.04). In conclusion, these results suggest that a QTL on chromosome 12q23-q24 influences the variation of plasma TG and HDL-C levels. Further investigation should confirm whether IGF1 or another nearby gene is responsible for the concomitant variation in TG and HDL-C levels.
为了确定一个常见的数量性状基因座（QTL）是否会影响空腹甘油三酯（TG）和高密度脂蛋白胆固醇（HDL-C）水平的变异，我们对99个白人家庭和101个黑人家庭中的654个多态性标记进行了双变量多点连锁分析。在两种条件下对表型进行了研究：基线时和20周运动训练干预后。在白人中，在位于IGF1基因（胰岛素样生长因子1，位于107厘摩）内的12号染色体q23-q24区域发现了基线时TG和HDL-C的全基因组最大双变量LOD分数为3.0（p = 0.00010）。这个双变量连锁峰明显高于同一染色体位置上任何一个性状的单变量连锁结果（对于TG，LOD = 2.07，p = 0.00108；对于HDL-C，LOD = 2.04，p = 0.00101）。基线TG和HDL-C水平之间的遗传相关性，残差为-0.14，QTL成分的为-0.33。此外，关联分析表明TG、HDL-C和IGF1显著相关（p = 0.04）。总之，这些结果表明12号染色体q23-q24上的一个QTL影响血浆TG和HDL-C水平的变异。进一步的研究应证实IGF1或另一个附近的基因是否是TG和HDL-C水平伴随变异的原因。
