Genetic variants link lower segregation of brain networks to higher blood pressure and worse cognition within the general aging population
Genetic variants link lower segregation of brain networks to higher blood pressure and worse cognition within the general aging population
Abstract The functional architecture of the brain is composed of distinct networks, where higher system segregation, i.e. greater differentiation of such functional networks, is associated with better cognitive performance. Aging and many neurological diseases have been associated with reduced system segregation and thus cognitive impairment. The genetic basis and risk factors of system segregation are largely unknown. Here, we present the first genome-wide association study of fMRI-assessed system segregation in 16,635 UK Biobank participants, identifying nine independent genomic loci. The 66 implicated genes were significantly downregulated in brain tissue and upregulated in vascular tissue. Of major vascular risk factors (Life’s Simple 7), blood pressure showed a robust genetic correlation with system segregation. Observational and Mendelian randomization analyses confirmed a unfavourable effect of higher blood pressure on system segregation and of lower system segregation on cognition. Replication analyses in 2,414 Rotterdam Study participants supported these conclusions.
Neitzel Julia、Malik Rainer、Muetzel Ryan、Zonneveld Hazel、Ikram M Arfan、Dichgans Martin、Ewers Michael、Georgakis Marios K、Franzmeier Nicolai、Rubinski Anna、Knol Maria J、Vernooij Meike W
Department of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre||Department of Epidemiology, Erasmus MC, University Medical CentreInstitute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMUDepartment of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical CentreDepartment of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre||Department of Epidemiology, Erasmus MC, University Medical CentreDepartment of Epidemiology, Erasmus MC, University Medical CentreInstitute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMU||German Center for Neurodegenerative Diseases (DZNE, Munich)||Munich Cluster for Systems Neurology (SyNergy)Institute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMUInstitute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMU||Center for Genomic Medicine, Massachusetts General Hospital, Harvard, Medical School||Program in Medical and Population Genetics, Broad Institute of Harvard and the Massachusetts Institute of TechnologyInstitute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMUInstitute for Stroke and Dementia Research (ISD), University Hospital Munich, Ludwig-Maximilians-University LMUDepartment of Epidemiology, Erasmus MC, University Medical CentreDepartment of Radiology and Nuclear Medicine, Erasmus MC, University Medical Centre||Department of Epidemiology, Erasmus MC, University Medical Centre
神经病学、精神病学遗传学基础医学
Neitzel Julia,Malik Rainer,Muetzel Ryan,Zonneveld Hazel,Ikram M Arfan,Dichgans Martin,Ewers Michael,Georgakis Marios K,Franzmeier Nicolai,Rubinski Anna,Knol Maria J,Vernooij Meike W.Genetic variants link lower segregation of brain networks to higher blood pressure and worse cognition within the general aging population[EB/OL].(2025-03-28)[2025-05-28].https://www.medrxiv.org/content/10.1101/2021.08.12.21261975.点此复制
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