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; CHIMGEN Consortium

doi:10.1016/j.isci.2023.108005

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

iScience. 2023 Sep 21;26(10):108005. doi: 10.1016/j.isci.2023.108005. eCollection 2023 Oct 20.

Authors

Hui Xue¹, Xiaojun Xu², Zhihan Yan³, Jingliang Cheng⁴, Longjiang Zhang⁵, Wenzhen Zhu⁶, Guangbin Cui⁷, Quan Zhang⁸, Shijun Qiu⁹, Zhenwei Yao¹⁰, Wen Qin¹, Feng Liu¹, Meng Liang¹¹, Jilian Fu¹, Qiang Xu¹, Jiayuan Xu¹, Yingying Xie¹, Peng Zhang¹², Wei Li¹², Caihong Wang⁴, Wen Shen¹³, Xiaochu Zhang¹⁴, Kai Xu¹⁵, Xi-Nian Zuo^{16

17}, Zhaoxiang Ye¹⁸, Yongqiang Yu¹⁹, Junfang Xian²⁰, Chunshui Yu^{1

21}; CHIMGEN Consortium

Affiliations

¹ Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
² Department of Radiology, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou 310009, China.
³ Department of Radiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
⁴ Department of Magnetic Resonance Imaging, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
⁵ Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, China.
⁶ Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁷ Functional and Molecular Imaging Key Lab of Shaanxi Province & Department of Radiology, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China.
⁸ Department of Radiology, Characteristic Medical Center of Chinese People's Armed Police Force, Tianjin 300162, China.
⁹ Department of Medical Imaging, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou 510405, China.
¹⁰ Department of Radiology, Huashan Hospital, Fudan University, Shanghai 200040, China.
¹¹ School of Medical Imaging and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University, Tianjin 300203, China.
¹² Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
¹³ Department of Radiology, Tianjin First Center Hospital, Tianjin 300192, China.
¹⁴ Division of Life Science and Medicine, University of Science & Technology of China, Hefei 230027, China.
¹⁵ Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, China.
¹⁶ Developmental Population Neuroscience Research Center at IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
¹⁷ Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
¹⁸ Department of Radiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin Medical University, Ministry of Education, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
¹⁹ Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China.
²⁰ Department of Radiology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
²¹ CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.

Abstract

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.

Keywords: Association analysis; Genomics; Medical imaging; Neuroanatomy; Neurogenetics.

Associated data

figshare/10.6084/m9.figshare.23551605.v1