Livshits Gregory, Kato Bernet S, Wilson Scott G, Spector Tim D
Tel Aviv University, Israel.
J Clin Endocrinol Metab. 2007 Aug;92(8):3171-6. doi: 10.1210/jc.2007-0418. Epub 2007 Jun 5.
Total lean body mass (LEAN-tot) is one of the three major components of body weight. Its deterioration is a risk factor for frailty. Despite this, there are few studies examining the contribution of genetic factors.
Our objective was to examine the contribution of genetic factors for LEAN-tot variation, including a genome-wide search for the genes.
Dual-energy x-ray absorptiometry measurements of LEAN-tot were obtained from each of the 3180 United Kingdom females (509 monozygotic and 1081 dizygotic twin pairs). Contribution of genetic factors was assessed using variance component analysis. A genome-wide linkage analysis was performed on the dizygotic twins using a modified version of the Haseman-Elston method.
Age, body height, total fat, and bone mass were correlated with LEAN-tot, and commonly explained 52% of the LEAN-tot variation. The crude heritability estimate was 74.0 +/- 4.0%, after adjustment for the aforementioned factors; 65.2 +/- 4.6% was attributable to independent genetic effects. Significant (P < 0.001) genetic correlations were found between LEAN-tot and bone mass, and LEAN-tot and total fat. Adjusted only for age, LEAN-tot showed no significant linkage. After adjustment for all covariates, significant linkage (LOD = 4.49 and 3.62) was observed at chromosome 12q24.3 and 14q22.3, respectively. Additional peaks of interest were on 7p15.3-15.1 (LOD = 2.86) and 8p22 (LOD = 2.83).
LEAN-tot measured by dual-energy x-ray absorptiometry is highly heritable, independent of other body measures. This first genomic search for genes associated with the lean component of body mass suggests significant linkage to quantitative trait loci on chromosomes 12 and 14.
总体瘦体重（LEAN-tot）是体重的三大主要组成部分之一。其恶化是衰弱的一个风险因素。尽管如此，很少有研究探讨遗传因素的作用。
我们的目的是研究遗传因素对LEAN-tot变异的作用，包括全基因组范围内寻找相关基因。
对3180名英国女性（509对同卵双胞胎和1081对异卵双胞胎）进行双能X线吸收法测量LEAN-tot。使用方差成分分析评估遗传因素的作用。对异卵双胞胎采用改良的Haseman-Elston方法进行全基因组连锁分析。
年龄、身高、总脂肪量和骨量与LEAN-tot相关，共同解释了LEAN-tot变异的52%。在对上述因素进行调整后，粗遗传度估计值为74.0±4.0%；65.2±4.6%归因于独立的遗传效应。在LEAN-tot与骨量、LEAN-tot与总脂肪量之间发现了显著的（P<0.001）遗传相关性。仅对年龄进行调整后，LEAN-tot未显示出显著的连锁关系。在对所有协变量进行调整后，分别在12号染色体q24.3和14号染色体q22.3观察到显著的连锁关系（LOD=4.49和3.62）。其他感兴趣的峰值位于7p15.3-15.1（LOD=2.86）和8p22（LOD=2.83）。
通过双能X线吸收法测量的LEAN-tot具有高度遗传性，独立于其他身体测量指标。首次对与体重瘦成分相关基因进行的基因组搜索表明，与12号和14号染色体上的数量性状位点存在显著连锁关系。
