Deng Hong-Wen, Deng Hongyi, Liu Yong-Jun, Liu Yao-Zhong, Xu Fu-Hua, Shen Hui, Conway Theresa, Li Jin-Long, Huang Qing-Yang, Davies K M, Recker Robert R
Osteoporosis Research Center, and Department of Biomedical Sciences, Creighton University, Omaha, NE, USA.
Am J Hum Genet. 2002 May;70(5):1138-51. doi: 10.1086/339934. Epub 2002 Mar 28.
Obesity is an increasingly serious health problem in the world. Body mass index (BMI), percentage fat mass, and body fat mass are important indices of obesity. For a sample of pedigrees that contains >10,000 relative pairs (including 1,249 sib pairs) that are useful for linkage analyses, we performed a whole-genome linkage scan, using 380 microsatellite markers to identify genomic regions that may contain quantitative-trait loci (QTLs) for obesity. Each pedigree was ascertained through a proband who has extremely low bone mass, which translates into a low BMI. A major QTL for BMI was identified on 2q14 near the marker D2S347 with a LOD score of 4.04 in two-point analysis and a maximum LOD score (MLS) of 4.44 in multipoint analysis. The genomic region near 2q14 also achieved an MLS >2.0 for percentage of fat mass and body fat mass. For the putative QTL on 2q14, as much as 28.2% of BMI variation (after adjustment for age and sex) may be attributable to this locus. In addition, several other genomic regions that may contain obesity-related QTLs are suggested. For example, 1p36 near the marker D1S468 may contain a QTL for BMI variation, with a LOD score of 2.75 in two-point analysis and an MLS of 2.09 in multipoint analysis. The genomic regions identified in this and earlier reports are compared for further exploration in extension studies that use larger samples and/or denser markers for confirmation and fine-mapping studies, to eventually identify major functional genes involved in obesity.
肥胖是全球日益严重的健康问题。体重指数（BMI）、体脂百分比和体脂量是肥胖的重要指标。对于一个包含超过10,000对亲属（包括1,249对同胞对）且可用于连锁分析的家系样本，我们进行了全基因组连锁扫描，使用380个微卫星标记来识别可能包含肥胖数量性状位点（QTL）的基因组区域。每个家系通过一个骨量极低（这转化为低BMI）的先证者确定。在标记D2S347附近的2q14上鉴定出一个BMI的主要QTL，两点分析中的LOD得分为4.04，多点分析中的最大LOD得分（MLS）为4.44。2q14附近的基因组区域在体脂百分比和体脂量方面也达到了MLS>2.0。对于2q14上的假定QTL，高达28.2%的BMI变异（在调整年龄和性别后）可能归因于该位点。此外，还提出了其他几个可能包含与肥胖相关QTL的基因组区域。例如，标记D1S468附近的1p36可能包含一个BMI变异的QTL，两点分析中的LOD得分为2.75，多点分析中的MLS为2.09。将本报告及早期报告中鉴定的基因组区域进行比较，以便在扩展研究中进一步探索，这些扩展研究使用更大的样本和/或更密集的标记进行确认和精细定位研究，最终确定参与肥胖的主要功能基因。
