A Structured Brain-wide and Genome-wide Association Study Using ADNI PET Images.

A Structured Brain-wide and Genome-wide Association Study Using ADNI PET Images.
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使用ADNI PET图像的结构化全脑和全基因组关联研究。

DOI:
10.1002/cjs.11605
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发表时间:
2021-03
期刊:
The Canadian journal of statistics = Revue canadienne de statistique
影响因子:
--
通讯作者:
Alzheimer’s Disease Neuroimaging Initiative
Alzheimer’s Disease Neuroimaging Initiative
中科院分区:
其他
文献类型:
--
作者:
Li Y;Nan B;Zhu J;Alzheimer’s Disease Neuroimaging Initiative

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提出了一种多阶段变量选择方法,用于结构化全脑和全基因组关联研究(brain-GWAS)中关联信号的检测。与传统的单体素到单SNP方法相比,我们的方法通过分别整合大脑和基因组中的解剖结构和基因分组结构,在选择重要信号方面更有效和强大。它避免了大量的多重比较,同时有效地控制了错误的发现。理论研究和数值模拟结果均表明了该方法的有效性。我们将所提出的方法应用于使用ADNI PET成像和基因组数据的脑GWAS。我们证实了先前报道的关联信号,并发现了几种新的SNP和基因,它们要么与脑葡萄糖代谢相关,要么与阿尔茨海默病状态显著相关。
A multi-stage variable selection method is introduced for detecting association signals in structured brain-wide and genome-wide association studies (brain-GWAS). Compared to conventional single-voxel-to-single-SNP approaches, our approach is more efficient and powerful in selecting the important signals by integrating anatomic and gene grouping structures in the brain and the genome, respectively. It avoids large number of multiple comparisons while effectively controls the false discoveries. Validity of the proposed approach is demonstrated by both theoretical investigation and numerical simulations. We apply the proposed method to a brain-GWAS using ADNI PET imaging and genomic data. We confirm previously reported association signals and also find several novel SNPs and genes that either are associated with brain glucose metabolism or have their association significantly modified by Alzheimer’s disease status.
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