Medial temporal lobe (MTL) consists of hippocampal subfields and neighboring cortices. These heterogeneous structures are differentially involved in memory, cognitive and emotional functions, and present nonuniformly distributed atrophy contributing to cognitive disorders. This study aims to examine how genetics influences Alzheimer's disease (AD) pathogenesis via MTL substructures by analyzing high-resolution magnetic resonance imaging (MRI) data. We performed genome-wide association study to examine the associations between 565,373 single nucleotide polymorphisms (SNPs) and 14 MTL substructure volumes. A novel association with right Brodmann area 36 volume was discovered in an ERC1 SNP (i.e., rs2968869). Further analyses on larger samples found rs2968869 to be associated with gray matter density and glucose metabolism measures in the right hippocampus, and disease status. Tissue-specific transcriptomic analysis identified the minor allele of rs2968869 (rs2968869-C) to be associated with reduced ERC1 expression in the hippocampus. All the findings indicated a protective role of rs2968869-C in AD. We demonstrated the power of high-resolution MRI and the promise of fine-grained MTL substructures for revealing the genetic basis of AD biomarkers.

中文翻译：

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内侧颞叶结构的体积 GWAS 使用 ADNI 高分辨率 T2 加权 MRI 数据识别 ERC1 位点

内侧颞叶 (MTL) 由海马亚区和邻近的皮质组成。这些异质结构不同程度地参与记忆、认知和情绪功能，并呈现导致认知障碍的不均匀分布的萎缩。本研究旨在通过分析高分辨率磁共振成像 (MRI) 数据，研究遗传学如何通过 MTL 子结构影响阿尔茨海默病 (AD) 的发病机制。我们进行了全基因组关联研究，以检查 565,373 个单核苷酸多态性 (SNP) 和 14 个 MTL 子结构卷之间的关联。在 ERC1 SNP（即 rs2968869）中发现了与右侧 Brodmann 区域 36 体积的新关联。对较大样本的进一步分析发现 rs2968869 与右侧海马体的灰质密度和葡萄糖代谢指标以及疾病状态有关。组织特异性转录组学分析发现 rs2968869 (rs2968869-C) 的次要等位基因与海马中 ERC1 表达降低有关。所有发现都表明 rs2968869-C 在 AD 中具有保护作用。我们展示了高分辨率 MRI 的力量以及细粒度 MTL 子结构在揭示 AD 生物标志物的遗传基础方面的前景。