Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.
Dense genotyping identifies and localizes multiple common and rare variant association signals in celiac disease.
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我们使用1000基因组计划试点CEU和额外的重新测序研究变异，对12041例乳糜泻病例和12228名对照进行了密集的基因分型，183个报告的免疫介导性疾病非人类白细胞抗原风险基因座。我们确定了13个新的具有全基因组意义的乳糜泻风险基因座，使已知的基因座(包括人类白细胞抗原)总数达到40个。在超过三分之一的这些基因座上发现了多个独立的关联信号，可归因于常见的、低频率的和罕见的遗传变异的组合。与以前获得的数据如HapMap3相比，我们在大样本中的密集基因分型提供了更高的连锁不平衡模式的分辨率，并建议将许多信号定位到更精细的区域。特别是，54个精细定位的信号中有29个似乎定位于特定的单基因--在某些情况下还定位于基因调控元件。我们定义了风险区域的复杂遗传架构，并提炼了风险信号，为阐明病因疾病机制提供了下一步。
We densely genotyped, using 1000 Genomes Project pilot CEU and additional re-sequencing study variants, 183 reported immune-mediated disease non-HLA risk loci in 12,041 celiac disease cases and 12,228 controls. We identified 13 new celiac disease risk loci at genome wide significance, bringing the total number of known loci (including HLA) to 40. Multiple independent association signals are found at over a third of these loci, attributable to a combination of common, low frequency, and rare genetic variants. In comparison with previously available data such as HapMap3, our dense genotyping in a large sample size provided increased resolution of the pattern of linkage disequilibrium, and suggested localization of many signals to finer scale regions. In particular, 29 of 54 fine-mapped signals appeared localized to specific single genes - and in some instances to gene regulatory elements. We define a complex genetic architecture of risk regions, and refine risk signals, providing a next step towards elucidating causal disease mechanisms.
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影响因子：
30.8
作者：
通讯作者：
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影响因子：
64.8
作者：
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DOI：
10.1126/science.1193032
发表时间：
2010-08-13
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
Genovese G;Friedman DJ;Ross MD;Lecordier L;Uzureau P;Freedman BI;Bowden DW;Langefeld CD;Oleksyk TK;Uscinski Knob AL;Bernhardy AJ;Hicks PJ;Nelson GW;Vanhollebeke B;Winkler CA;Kopp JB;Pays E;Pollak MR
通讯作者：
Pollak MR
影响因子：
30.8
作者：
通讯作者：
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影响因子：
30.8
作者：
通讯作者：
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