A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context

Background: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among geneti...

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Main Authors: Na Luo, Jing Sui, Jiayu Chen, Fuquan Zhang, Lin Tian, Dongdong Lin, Ming Song, Vince D. Calhoun, Yue Cui, Victor M. Vergara, Fanfan Zheng, Jingyu Liu, Zhenyi Yang, Nianming Zuo, Lingzhong Fan, Kaibin Xu, Shengfeng Liu, Jian Li, Yong Xu, Sha Liu, Luxian Lv, Jun Chen, Yunchun Chen, Hua Guo, Peng Li, Lin Lu, Ping Wan, Huaning Wang, Huiling Wang, Hao Yan, Jun Yan, Yongfeng Yang, Hongxing Zhang, Dai Zhang, Tianzi Jiang
Format: Article
Language:English
Published: Elsevier 2018-11-01
Series:EBioMedicine
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396418304195
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language English
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author Na Luo
Jing Sui
Jiayu Chen
Fuquan Zhang
Lin Tian
Dongdong Lin
Ming Song
Vince D. Calhoun
Yue Cui
Victor M. Vergara
Fanfan Zheng
Jingyu Liu
Zhenyi Yang
Nianming Zuo
Lingzhong Fan
Kaibin Xu
Shengfeng Liu
Jian Li
Yong Xu
Sha Liu
Luxian Lv
Jun Chen
Yunchun Chen
Hua Guo
Peng Li
Lin Lu
Ping Wan
Huaning Wang
Huiling Wang
Hao Yan
Jun Yan
Yongfeng Yang
Hongxing Zhang
Dai Zhang
Tianzi Jiang
spellingShingle Na Luo
Jing Sui
Jiayu Chen
Fuquan Zhang
Lin Tian
Dongdong Lin
Ming Song
Vince D. Calhoun
Yue Cui
Victor M. Vergara
Fanfan Zheng
Jingyu Liu
Zhenyi Yang
Nianming Zuo
Lingzhong Fan
Kaibin Xu
Shengfeng Liu
Jian Li
Yong Xu
Sha Liu
Luxian Lv
Jun Chen
Yunchun Chen
Hua Guo
Peng Li
Lin Lu
Ping Wan
Huaning Wang
Huiling Wang
Hao Yan
Jun Yan
Yongfeng Yang
Hongxing Zhang
Dai Zhang
Tianzi Jiang
A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
EBioMedicine
author_facet Na Luo
Jing Sui
Jiayu Chen
Fuquan Zhang
Lin Tian
Dongdong Lin
Ming Song
Vince D. Calhoun
Yue Cui
Victor M. Vergara
Fanfan Zheng
Jingyu Liu
Zhenyi Yang
Nianming Zuo
Lingzhong Fan
Kaibin Xu
Shengfeng Liu
Jian Li
Yong Xu
Sha Liu
Luxian Lv
Jun Chen
Yunchun Chen
Hua Guo
Peng Li
Lin Lu
Ping Wan
Huaning Wang
Huiling Wang
Hao Yan
Jun Yan
Yongfeng Yang
Hongxing Zhang
Dai Zhang
Tianzi Jiang
author_sort Na Luo
title A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
title_short A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
title_full A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
title_fullStr A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
title_full_unstemmed A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in context
title_sort schizophrenia-related genetic-brain-cognition pathway revealed in a large chinese populationresearch in context
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2018-11-01
description Background: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset. Methods: Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways. Findings: One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance. Interpretation: This study has not only verified the impaired imaging-genetic association in schizophrenia, but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia. Keywords: Schizophrenia, Multimodal fusion, Genetic-brain-cognition pathway, Working memory, Mediation analysis
url http://www.sciencedirect.com/science/article/pii/S2352396418304195
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spelling doaj-c5a29abf3dd64bde8c4dab9f4bb2423c2020-11-25T02:53:07ZengElsevierEBioMedicine2352-39642018-11-0137471482A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese PopulationResearch in contextNa Luo0Jing Sui1Jiayu Chen2Fuquan Zhang3Lin Tian4Dongdong Lin5Ming Song6Vince D. Calhoun7Yue Cui8Victor M. Vergara9Fanfan Zheng10Jingyu Liu11Zhenyi Yang12Nianming Zuo13Lingzhong Fan14Kaibin Xu15Shengfeng Liu16Jian Li17Yong Xu18Sha Liu19Luxian Lv20Jun Chen21Yunchun Chen22Hua Guo23Peng Li24Lin Lu25Ping Wan26Huaning Wang27Huiling Wang28Hao Yan29Jun Yan30Yongfeng Yang31Hongxing Zhang32Dai Zhang33Tianzi Jiang34Brainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; The Mind Research Network & LBERI, Albuquerque, NM 87106, USA; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; Corresponding authors at: Brainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China.The Mind Research Network & LBERI, Albuquerque, NM 87106, USAWuxi Mental Health Center, Wuxi 214000, ChinaWuxi Mental Health Center, Wuxi 214000, ChinaThe Mind Research Network & LBERI, Albuquerque, NM 87106, USABrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaThe Mind Research Network & LBERI, Albuquerque, NM 87106, USA; Department of Electrical and Computer Engineer, The University of New, Albuquerque, NM 87131, USABrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaThe Mind Research Network & LBERI, Albuquerque, NM 87106, USABrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaThe Mind Research Network & LBERI, Albuquerque, NM 87106, USABrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, ChinaDepartment of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Psychiatry, First Clinical Medical College, First Hospital of Shanxi Medical University, Taiyuan 030000, ChinaDepartment of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China,Department of Radiology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaDepartment of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, ChinaZhumadian Psychiatric Hospital, Zhumadian 463000, ChinaInstitute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, ChinaInstitute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, ChinaZhumadian Psychiatric Hospital, Zhumadian 463000, ChinaDepartment of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, ChinaDepartment of Radiology, Renmin Hospital of Wuhan University, Wuhan 430060, ChinaInstitute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, ChinaInstitute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, ChinaDepartment of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Henan Key Lab of Biological Psychiatry, Xinxiang Medical University, Xinxiang 453002, China,; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, ChinaDepartment of Psychiatry, Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang 453002, China; Department of Psychology, Xinxiang Medical University, Xinxiang 453002, ChinaInstitute of Mental Health, Peking University Sixth Hospital, Beijing 100191, China; Key Laboratory of Mental Health, Ministry of Health, Peking University, Beijing 100191, China; Center for Life Sciences, PKU-IDG, McGovern Institute for Brain Research, Peking University, Beijing 100871, ChinaBrainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China; Queensland Brain Institute, University of Queensland, Brisbane, QLD 4072, Australia; CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China; Corresponding authors at: Brainnetome Center and National Laboratory of Pattern Recognition, Chinese Academy of Sciences, Institute of Automation, Beijing 100190, China.Background: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset. Methods: Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways. Findings: One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance. Interpretation: This study has not only verified the impaired imaging-genetic association in schizophrenia, but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia. Keywords: Schizophrenia, Multimodal fusion, Genetic-brain-cognition pathway, Working memory, Mediation analysishttp://www.sciencedirect.com/science/article/pii/S2352396418304195