Kraja Aldi T, Rao Dabeeru C, Weder Alan B, Cooper Richard, Curb J David, Hanis Craig L, Turner Stephen T, de Andrade Mariza, Hsiung Chao Agnes, Quertermous Thomas, Zhu Xiaofeng, Province Michael A
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63123, USA.
Hypertension. 2005 Oct;46(4):751-7. doi: 10.1161/01.HYP.0000184249.20016.bb. Epub 2005 Sep 19.
Genome-wide variance components linkage analysis was performed on 4 latent factors underlying metabolic syndrome derived from 10 risk factors. The latent factors represent obesity and insulin, blood pressure, lipids and insulin, and central obesity. The metabolic syndrome factor scores were derived in 4 ethnic groups recruited in 3 Networks of the Family Blood Pressure Program: GENOA (blacks, Hispanics, and whites), HyperGEN (blacks and whites), SAPPHIRe (Asians). Heritabilities of metabolic syndrome factors ranged from 66% for obesity and insulin to 11% for blood pressure factor. We observed higher heritabilities for obesity and insulin, and lipids and insulin, whereas those for blood pressure and central obesity were smaller. Linkage analysis detected two major quantitative trait loci. One of them linked to the obesity and insulin factor with a lod score of 3.94 (P=0.00001, marker GATA11A06, D18S53, 41.24 cM) at marker positions linkage (lod 4.71, at 46.84 cM at 1-cM-apart distances linkage), located on chromosome 18p11.21 in GENOA black. The other linked to the blood pressure factor with a lod score of 3.22 (P=0.000059, marker GATA49C09, D17S1290, 82 cM) at marker positions linkage (lod 3.56, at 84.63 cM for 1 cM apart distances linkage) located on chromosome 17q23.1 in Hispanics. These quantitative trait loci, together with 4 additional ones with lod scores >2.5, and 30 additional ones with lod score >1.7, offer hope for dissecting the genetic architecture of metabolic syndrome with beneficial implications for molecular diagnosis, prognosis, and in potential medical intervention.
对源自10个风险因素的代谢综合征的4个潜在因素进行了全基因组方差成分连锁分析。这些潜在因素代表肥胖与胰岛素、血压、脂质与胰岛素以及中心性肥胖。代谢综合征因子得分是在家庭血压项目的3个网络中招募的4个种族群体中得出的：热那亚研究（黑人、西班牙裔和白人）、高血压遗传研究（黑人和白人）、蓝宝石研究（亚洲人）。代谢综合征各因素的遗传率范围从肥胖与胰岛素因素的66%到血压因素的11%。我们观察到肥胖与胰岛素以及脂质与胰岛素的遗传率较高，而血压和中心性肥胖的遗传率较低。连锁分析检测到两个主要的数量性状位点。其中一个与肥胖和胰岛素因素连锁，在连锁标记位置（lod值为4.71，在相距1厘摩的距离连锁时位于46.84厘摩处）的lod值为3.94（P = 0.00001，标记GATA11A06，D18S53，41.24厘摩），位于热那亚黑人的18号染色体p11.21区域。另一个与血压因素连锁，在连锁标记位置（lod值为3.56，在相距1厘摩的距离连锁时位于84.63厘摩处）的lod值为3.22（P = 0.000059，标记GATA49C09，D17S1290，82厘摩），位于西班牙裔的17号染色体q23.1区域。这些数量性状位点，连同另外4个lod值>2.5的位点，以及另外30个lod值>1.7的位点，为剖析代谢综合征的遗传结构带来了希望，对分子诊断、预后以及潜在的医学干预具有有益的意义。
