Qiong Wu, Yuan Zhang, Xiaoqi Huang, Tianzhou Ma, L Elliot Hong, Peter Kochunov, Shuo Chen
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引用次数: 0
摘要
成像与遗传学数据的联合分析有助于系统地研究遗传对大脑结构和功能的空间特异性影响。我们的研究重点是体素全基因组关联分析,其中可能涉及数以万亿计的单核苷酸多态性(SNP)-体素对。我们试图找出 SNP-象素对的潜在有组织关联模式,并了解大脑成像特征的多基因和多效应网络。我们为系统关联模式提出了一种双环图结构(即一组 SNP 与一簇体素高度相关)。接下来,我们开发了检测潜在 SNP-体素双环图的计算策略和用于统计检验的推理模型。我们进一步提供了理论结果,以保证我们的计算算法和统计推断的准确性。我们通过大量的模拟研究验证了我们的方法,然后将其应用于从人类连接组项目的 1052 名参与者那里收集到的全基因组遗传和体素级白质完整性数据。结果表明,多个遗传位点影响了胼胝体的脾和玄的白质完整性测量。
A multivariate to multivariate approach for voxel-wise genome-wide association analysis.
The joint analysis of imaging-genetics data facilitates the systematic investigation of genetic effects on brain structures and functions with spatial specificity. We focus on voxel-wise genome-wide association analysis, which may involve trillions of single nucleotide polymorphism (SNP)-voxel pairs. We attempt to identify underlying organized association patterns of SNP-voxel pairs and understand the polygenic and pleiotropic networks on brain imaging traits. We propose a bi-clique graph structure (ie, a set of SNPs highly correlated with a cluster of voxels) for the systematic association pattern. Next, we develop computational strategies to detect latent SNP-voxel bi-cliques and an inference model for statistical testing. We further provide theoretical results to guarantee the accuracy of our computational algorithms and statistical inference. We validate our method by extensive simulation studies, and then apply it to the whole genome genetic and voxel-level white matter integrity data collected from 1052 participants of the human connectome project. The results demonstrate multiple genetic loci influencing white matter integrity measures on splenium and genu of the corpus callosum.
期刊介绍:
The journal aims to influence practice in medicine and its associated sciences through the publication of papers on statistical and other quantitative methods. Papers will explain new methods and demonstrate their application, preferably through a substantive, real, motivating example or a comprehensive evaluation based on an illustrative example. Alternatively, papers will report on case-studies where creative use or technical generalizations of established methodology is directed towards a substantive application. Reviews of, and tutorials on, general topics relevant to the application of statistics to medicine will also be published. The main criteria for publication are appropriateness of the statistical methods to a particular medical problem and clarity of exposition. Papers with primarily mathematical content will be excluded. The journal aims to enhance communication between statisticians, clinicians and medical researchers.