Sale M M, Freedman B I, Hicks P J, Williams A H, Langefeld C D, Gallagher C J, Bowden D W, Rich S S
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem NC 27157, USA.
Ann Hum Genet. 2005 Sep;69(Pt 5):517-27. doi: 10.1046/j.1529-8817.2005.00176.x.
Height and body mass index (BMI) have high heritability in most studies. High BMI and reduced height are well-recognized as important risk factors for a number of cardiovascular diseases. We investigated these phenotypes in African American families originally ascertained for studies of linkage with type 2 diabetes using self-reported height and weight. We conducted a genome wide scan in 221 families containing 580 individuals and 672 relative pairs of African American descent. Estimates of heritability and support for linkage were assessed by genetic variance component analyses using SOLAR software. The estimated heritabilities for height and BMI were 0.43 and 0.64, respectively. We have identified major loci contributing to variation in height on chromosomes 15 (LOD = 2.61 at 35 cM, p = 0.0004), 3 (LOD = 1.82 at 84 cM, p = 0.0029), 8 (LOD = 1.92 at 135 cM, p = 0.0024) and 17 (LOD = 1.70 at 110 cM, p = 0.0044). A broad region on chromosome 4 supported evidence of linkage to variation in BMI, with the highest LOD = 2.66 at 168 cM (p = 0.0005). Two height loci and two BMI loci appear to confirm the existence of quantitative trait loci previously identified by other studies, providing important replicative data to allow further resolution of linkage regions suitable for positional cloning of these cardiovascular disease risk loci.
在大多数研究中,身高和体重指数(BMI)具有较高的遗传度。高BMI和身高降低是多种心血管疾病公认的重要危险因素。我们以最初因2型糖尿病连锁研究而确定的非裔美国家庭为研究对象,使用自我报告的身高和体重调查了这些表型。我们对221个家庭进行了全基因组扫描,这些家庭包含580名个体和672对非裔美国人后裔的亲属对。使用SOLAR软件通过遗传方差成分分析评估遗传度估计值和连锁支持度。身高和BMI的估计遗传度分别为0.43和0.64。我们在15号染色体(35 cM处LOD = 2.61,p = 0.0004)、3号染色体(84 cM处LOD = 1.82,p = 0.0029)、8号染色体(135 cM处LOD = 1.92,p = 0.0024)和17号染色体(110 cM处LOD = 1.70,p = 0.0044)上确定了导致身高变异的主要基因座。4号染色体上的一个广泛区域支持与BMI变异连锁的证据,在168 cM处LOD最高为2.66(p = 0.0005)。两个身高基因座和两个BMI基因座似乎证实了先前其他研究中确定的数量性状基因座的存在,提供了重要的重复数据,以便进一步解析适合这些心血管疾病风险基因座定位克隆的连锁区域。