The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study.: I.: An autosomal genome scan for genes that predispose to type 2 diabetes
The Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study.: I.: An autosomal genome scan for genes that predispose to type 2 diabetes
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DOI：
10.1016/s0002-9297(07)62948-6
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发表时间：
2000-11-01
影响因子：
9.8
通讯作者：
Boehnke, M
中科院分区：
文献类型：
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作者：
Ghosh, S;Watanabe, RM;Boehnke, M
我们对719对患有2型糖尿病的芬兰同胞进行了平均分辨率为8厘米的基因组扫描。我们最强的结果是20号染色体，我们观察到加权最大LOD评分（MLS）在距pter 69.5 cM的地图位置为2.15，次级加权LOD评分峰值为2.04，在56.5 cM和17.5 cM处为1.99。第二大最大最小值是11号染色体（在84.0 cM处的最大最小值为1.75），其次是2号染色体（在5.5 cM处的最大最小值为0.87）、10号染色体（在75.0 cM处的最大最小值为0.77）和6号染色体（在112.5 cM处的最大最小值为0.61），所有这些都是在相加模型下进行的。当2号染色体为8.5 cM时，20号染色体的MLS在69.0 cM时增加到5.50 （P = 0.0014）。一项基于具有高或低糖尿病相关数量性状的家族的有序亚群分析得出的结果支持6号和10号染色体上可能存在易患疾病的基因。使用微卫星标记数据的全基因组连锁不平衡分析显示了与D22S423相关的强有力证据（P = 0.007）。进一步的分析正在进行，以确认和完善这些假定的糖尿病易感基因的位置。
We performed a genome scan at an average resolution of 8 cM in 719 Finnish sib pairs with type 2 diabetes. Our strongest results are for chromosome 20, where we observe a weighted maximum LOD score (MLS) of 2.15 at map position 69.5 cM from pter and secondary weighted LOD-score peaks of 2.04 at 56.5 cM and 1.99 at 17.5 cM. Our next largest MLS is for chromosome 11 (MLS = 1.75 at 84.0 cM), followed by chromosomes 2 (MLS = 0.87 at 5.5 cM), 10 (MLS = 0.77 at 75.0 cM), and 6 (MLS = 0.61 at 112.5 cM), all under an additive model. When we condition on chromosome 2 at 8.5 cM, the MLS for chromosome 20 increases to 5.50 at 69.0 cM (P = .0014). An ordered-subsets analysis based on families with high or low diabetes-related quantitative traits yielded results that support the possible existence of disease-predisposing genes on chromosomes 6 and 10. Genomewide linkage-disequilibrium analysis using microsatellite marker data revealed strong evidence of association for D22S423 (P = .00007). Further analyses are being carried out to confirm and to refine the location of these putative diabetes-predisposing genes.