iScience (Oct 2023)

Genome-wide association study of hippocampal blood-oxygen-level-dependent-cerebral blood flow correlation in Chinese Han population

  • Hui Xue,
  • Xiaojun Xu,
  • Zhihan Yan,
  • Jingliang Cheng,
  • Longjiang Zhang,
  • Wenzhen Zhu,
  • Guangbin Cui,
  • Quan Zhang,
  • Shijun Qiu,
  • Zhenwei Yao,
  • Wen Qin,
  • Feng Liu,
  • Meng Liang,
  • Jilian Fu,
  • Qiang Xu,
  • Jiayuan Xu,
  • Yingying Xie,
  • Peng Zhang,
  • Wei Li,
  • Caihong Wang,
  • Wen Shen,
  • Xiaochu Zhang,
  • Kai Xu,
  • Xi-Nian Zuo,
  • Zhaoxiang Ye,
  • Yongqiang Yu,
  • Junfang Xian,
  • Chunshui Yu

Journal volume & issue
Vol. 26, no. 10
p. 108005

Abstract

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Summary: Correlation between blood-oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) has been used as an index of neurovascular coupling. Hippocampal BOLD-CBF correlation is associated with neurocognition, and the reduced correlation is associated with neuropsychiatric disorders. We conducted the first genome-wide association study of the hippocampal BOLD-CBF correlation in 4,832 Chinese Han subjects. The hippocampal BOLD-CBF correlation had an estimated heritability of 16.2–23.9% and showed reliable genome-wide significant association with a locus at 3q28, in which many variants have been linked to neuroimaging and cerebrospinal fluid markers of Alzheimer’s disease. Gene-based association analyses showed four significant genes (GMNC, CRTC2, DENND4B, and GATAD2B) and revealed enrichment for mast cell calcium mobilization, microglial cell proliferation, and ubiquitin-related proteolysis pathways that regulate different cellular components of the neurovascular unit. This is the first unbiased identification of the association of hippocampal BOLD-CBF correlation, providing fresh insights into the genetic architecture of hippocampal neurovascular coupling.

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