Independent confirmation of a major locus for obesity on chromosome 10
Independent confirmation of a major locus for obesity on chromosome 10
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DOI：
10.1210/jc.85.8.2962
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发表时间：
2000-08-01
影响因子：
5.8
通讯作者：
Hebebrand, J
中科院分区：
文献类型：
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作者：
Hinney, A;Ziegler, A;Hebebrand, J
在全基因组扫描中获得的复杂表型的连锁结果需要在独立的样本中得到确认。最近，肥胖与染色体10P12的最大多点LOD得分为4.85的连锁被报道使用了一种受影响的同胞配对方法，包括核心家庭，其中成人指数病例的BMI大于或等于40 kg/m(2)，并且至少另外一个兄弟姐妹的BMI大于或等于27 kg/m(2)(Hager等人，1998，NAT Genet 20：304-8)。为了试图复制这一连锁发现，我们在总共386个个体中对从10p13到10q11大约23 cM的11个标记进行了基因分型，这些标记来自93个核心家庭，这些核心家庭有两个或更多年轻的肥胖子女，他们的BMI大于或等于90岁百分位数。使用极端协调同胞配对方法的最高多点最大似然二项式(MLB)LOD得分为2.32，其中一个同胞的BMI大于或等于第95个百分位数，其他同胞的BMI大于或等于第90个百分位数。6个标记的标称p值为0.05，其中标记TCF8的最高两点mlb-lod得分为2.45(标称p=0.0004)。对最常见的亲本等位基因的传递不平衡检验没有得到标称的p值&0.05。连锁结果证实，在10号染色体着丝粒附近的区域存在一个肥胖的主要易感基因。
Linkage results obtained in genome-wide scans for complex phenotypes require confirmation in independent samples. Recently, linkage of obesity to chromosome 10p12 with a maximal multipoint LOD score of 4.85 was reported upon use of an affected sib-pair approach including nuclear families in which the adult index case had a BMI greater than or equal to 40 kg/m(2) and at least one further sibling had a BMI greater than or equal to 27 kg/m(2) (Hager et al., 1998, Nat Genet 20:304-8). To attempt to replicate this linkage finding we genotyped 11 markers spanning approximately 23 cM from 10p13 to 10q11 in a total of 386 individuals stemming from 93 nuclear families with two or more young obese offspring with a BMI greater than or equal to 90th age percentile. The highest multipoint maximum likelihood binomial (MLB) LOD score using the extreme concordant sib-pair approach in which one sib had a BMI greater than or equal to 95th percentile, and other sibs a BMI greater than or equal to 90th percentile was 2.32. Six markers yielded nominal p-values < 0.05, the highest two point MLB-LOD score of 2.45 (nominal p = 0.0004) was obtained for the marker TCF8. Transmission disequilibrium tests for the most frequent parental allele yielded no nominal p-value < 0.05. The linkage results confirm the presence of a major susceptibility locus for obesity in a region near the centromere on chromosome 10.