Association of FTO variants with BMI and fat mass in the self-contained population of Sorbs in Germany
Association of FTO variants with BMI and fat mass in the self-contained population of Sorbs in Germany
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DOI：
10.1038/ejhg.2009.107
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发表时间：
2010-01-01
影响因子：
5.2
通讯作者：
Stumvoll, Michael
中科院分区：
文献类型：
--
作者：
Toenjes, Anke;Zeggini, Eleftheria;Stumvoll, Michael
FTO基因中常见变异与体重、肥胖和体重指数（BMI）之间的关联现已得到广泛复制。虽然致病变异体尚未被鉴定，但它很可能定位在FTO内含子1的47 kb区域内。我们在索布族人群中进行了全基因组关联研究，并评估了FTO变异体与德国斯拉夫裔居民的BMI和脂肪量之间的关系。在948个Sorb人的样本中，我们可以重复先前报道的内含子1 SNP与BMI的相关性（例如，rs 8050136的P值为0.003，β =0.02）。然而，使用全基因组关联数据，我们还检测到第二个独立信号映射到内含子2/3中距离最初报道的SNP约40-60 kb的区域（例如，对于rs 17818902，与BMI的关联P值=0.0006，β =-0.03，与脂肪量的关联P值-0.0018，β（-）-0.079）。两个信号在条件分析中保持独立关联。总之，我们扩展了FTO变异体与BMI相关的证据，通过鉴定第二个独立于先前描述的易感性等位基因。虽然这些调查结果的进一步统计分析受到索布族隔离的有限规模的阻碍，这些调查结果应该鼓励其他群体寻求FTO（和其他已建立的易感基因座）内的替代易感性变异体，利用不同的突变和/或人口统计学历史的人群分析所提供的机会。European Journal of Human Genetics（2010）18，104-110; doi：10.1038/ejhg.2009.107; 2009年7月8日在线发表
The association between common variants in the FTO gene with weight, adiposity and body mass index (BMI) has now been widely replicated. Although the causal variant has yet to be identified, it most likely maps within a 47 kb region of intron 1 of FTO. We performed a genome-wide association study in the Sorbian population and evaluated the relationships between FTO variants and BMI and fat mass in this isolate of Slavonic origin resident in Germany. In a sample of 948 Sorbs, we could replicate the earlier reported associations of intron 1 SNPs with BMI (eg, P-value-0.003, beta=0.02 for rs8050136). However, using genome-wide association data, we also detected a second independent signal mapping to a region in intron 2/3 about 40-60 kb away from the originally reported SNPs (eg, for rs17818902 association with BMI P-value=0.0006, beta=-0.03 and with fat mass P-value-0.0018, beta(-) -0.079). Both signals remain independently associated in the conditioned analyses. In conclusion, we extend the evidence that FTO variants are associated with BMI by putatively identifying a second susceptibility allele independent of that described earlier. Although further statistical analysis of these findings is hampered by the finite size of the Sorbian isolate, these findings should encourage other groups to seek alternative susceptibility variants within FTO (and other established susceptibility loci) using the opportunities afforded by analyses in populations with divergent mutational and/or demographic histories. European Journal of Human Genetics (2010) 18, 104-110; doi:10.1038/ejhg.2009.107; published online 8 July 2009