Genetic Insights into Brain Morphology: a Genome-Wide Association Study of Cortical Thickness and T₁-Weighted MRI Gray Matter-White Matter Intensity Contrast.

IF 2.7 4区医学 Q2 COMPUTER SCIENCE, INTERDISCIPLINARY APPLICATIONS

Neuroinformatics Pub Date : 2025-04-01 DOI:10.1007/s12021-025-09722-9

Nicholas J Kim, Nahian F Chowdhury, Kenneth H Buetow, Paul M Thompson, Andrei Irimia

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Abstract

In T₁-weighted magnetic resonance imaging (MRI), cortical thickness (CT) and gray-white matter contrast (GWC) capture brain morphological traits and vary with age-related disease. To gain insight into genetic factors underlying brain structure and dynamics observed during neurodegeneration, this genome-wide association study (GWAS) quantifies the relationship between single nucleotide polymorphisms (SNPs) and both CT and GWC in UK Biobank participants (N = 43,002). To our knowledge, this is the first GWAS to investigate the genetic determinants of cortical T₁-MRI GWC in humans. We found 251 SNPs associated with CT or GWC for at least 1% of cortical locations, including 42 for both CT and GWC; 127 for only CT; and 82 for only GWC. Identified SNPs include rs1080066 (THSB1, featuring the strongest association with both CT and GWC), rs13107325 (SLC39A8, linked to CT at the largest number of cortical locations), and rs864736 (KCNK2, associated with GWC at the largest number of cortical locations). Dimensionality reduction reveals three major gene ontologies constraining CT (neural signaling, ion transport, cell migration) and four constraining GWC (neural cell development, cellular homeostasis, tissue repair, ion transport). Our findings provide insight into genetic determinants of GWC and CT, highlighting pathways associated with brain anatomy and dynamics of neurodegeneration. These insights can assist the development of gene therapies and treatments targeting brain diseases.

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大脑形态学的遗传洞察：皮质厚度和t1加权MRI灰质-白质强度对比的全基因组关联研究。

在t1加权磁共振成像（MRI）中，皮质厚度（CT）和灰质对比（GWC）捕捉大脑形态特征，并随年龄相关疾病而变化。为了深入了解神经退行性变过程中观察到的大脑结构和动态的遗传因素，这项全基因组关联研究（GWAS）量化了英国生物银行参与者（N = 43,002）的单核苷酸多态性（snp）与CT和GWC之间的关系。据我们所知，这是第一个研究人类皮层T1-MRI GWC遗传决定因素的GWAS。我们发现251个snp与至少1%的皮质部位的CT或GWC相关，其中42个与CT和GWC都相关；仅CT 127；仅GWC为82。已鉴定的snp包括rs1080066 （THSB1，与CT和GWC的关联最强）、rs13107325 （SLC39A8，与CT在皮质位置的关联最多）和rs864736 （KCNK2，与GWC在皮质位置的关联最多）。降维揭示了制约CT的三个主要基因本体（神经信号、离子转运、细胞迁移）和制约GWC的四个主要基因本体（神经细胞发育、细胞稳态、组织修复、离子转运）。我们的研究结果为GWC和CT的遗传决定因素提供了见解，突出了与脑解剖和神经变性动力学相关的途径。这些见解可以帮助开发基因疗法和针对脑部疾病的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroinformatics 医学-计算机：跨学科应用

CiteScore

6.00

自引率

6.70%

发文量

审稿时长

3 months

期刊介绍： Neuroinformatics publishes original articles and reviews with an emphasis on data structure and software tools related to analysis, modeling, integration, and sharing in all areas of neuroscience research. The editors particularly invite contributions on: (1) Theory and methodology, including discussions on ontologies, modeling approaches, database design, and meta-analyses; (2) Descriptions of developed databases and software tools, and of the methods for their distribution; (3) Relevant experimental results, such as reports accompanie by the release of massive data sets; (4) Computational simulations of models integrating and organizing complex data; and (5) Neuroengineering approaches, including hardware, robotics, and information theory studies.