A genomewide linkage scan for quantitative-trait loci for obesity phenotypes
A genomewide linkage scan for quantitative-trait loci for obesity phenotypes
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DOI：
10.1086/339934
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发表时间：
2002-05-01
影响因子：
9.8
通讯作者：
Recker, RR
中科院分区：
文献类型：
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作者：
Deng, HW;Deng, HY;Recker, RR
肥胖是世界上一个日益严重的健康问题。体重指数(BMI)、体脂质量百分比和体脂质量是肥胖的重要指标。对于一个包含10,000对对连锁分析有用的亲属对(包括1,249对同胞对)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的数量性状基因座(QTL)的基因组区域。每个家系都是通过骨量极低的先证者确定的，这意味着体重指数很低。在标记D2S347附近的2Q14上定位了一个主效QTL，两点分析的LOD得分为4.04，多点分析的最大LOD得分为4.44。2Q14附近的基因组区域的脂肪质量百分比和体脂质量也达到了MLS>；2.0。对于第2个Q14上的推测QTL，高达28.2%的BMI变异(调整了年龄和性别后)可能归因于该基因座。此外，还提出了其他几个可能包含与肥胖相关的QTL的基因组区域。例如，标记D1S468附近的1p36可能包含BMI变异的QTL，两点分析的LOD得分为2.75，多点分析的MLS为2.09。这份报告和之前的报告中确定的基因组区域进行了比较，以便在扩展研究中进行进一步的探索，这些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，最终确定与肥胖有关的主要功能基因。
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.