Aissani Brahim, Perusse Louis, Lapointe Gilles, Chagnon Yvon C, Bouchard Luigi, Walts Brandon, Bouchard Claude
Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
Obesity (Silver Spring). 2006 Sep;14(9):1605-15. doi: 10.1038/oby.2006.185.
To explore a quantitative trait locus (QTL) on human chromosome 1q affecting BMI, adiposity, and fat-free mass phenotypes in the Quebec Family Study cohort.
Non-parametric sibpair and variance component linkage analyses and family-based association studies were performed with a dense set of chromosome 1q43 microsatellites and single-nucleotide polymorphism markers in 885 adult individuals.
Linkage was observed between marker D1S184 and BMI (p = 0.0004) and with body fat mass or percentage body fat (p < or = 0.0003), but no linkage was detected with fat-free mass. Furthermore, significant linkages (p < 0.0001) were achieved with subsamples of sibpairs at both ends of phenotype distributions. Association studies with quantitative transmission disequilibrium tests refined the linkage to a region overlapping the regulator of G-protein signaling 7 (RGS7) gene and extending to immediate upstream gene loci.
The present study indicates that the QTL on chromosome 1q43 specifically affects total adiposity and provides a genetic mapping framework for the dissection of this adiposity locus.
在魁北克家族研究队列中探索人类1号染色体上影响体重指数（BMI）、肥胖度和去脂体重表型的数量性状基因座（QTL）。
对885名成年个体，采用1号染色体1q43微卫星和单核苷酸多态性标记的密集集合，进行非参数同胞对和方差成分连锁分析以及基于家系的关联研究。
观察到标记D1S184与BMI（p = 0.0004）以及体脂肪量或体脂百分比之间存在连锁（p≤0.0003），但未检测到与去脂体重的连锁。此外，在表型分布两端的同胞对亚样本中实现了显著连锁（p < 0.0001）。使用定量传递不平衡检验的关联研究将连锁区域细化到与G蛋白信号调节因子7（RGS7）基因重叠并延伸至紧邻上游基因座的区域。
本研究表明1号染色体1q43上的QTL特异性影响总体肥胖度，并为剖析该肥胖基因座提供了遗传定位框架。
