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Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.
Mei, Hao; Simino, Jeannette; Li, Lianna; Jiang, Fan; Bis, Joshua C; Davies, Gail; Hill, W David; Xia, Charley; Gudnason, Vilmundur; Yang, Qiong; Lahti, Jari; Smith, Jennifer A; Kirin, Mirna; De Jager, Philip; Armstrong, Nicola J; Ghanbari, Mohsen; Kolcic, Ivana; Moran, Christopher; Teumer, Alexander; Sargurupremraj, Murali; Mahmud, Shamsed; Fornage, Myriam; Zhao, Wei; Satizabal, Claudia L; Polasek, Ozren; Räikkönen, Katri; Liewald, David C; Homuth, Georg; Callisaya, Michele; Mather, Karen A; Windham, B Gwen; Zemunik, Tatijana; Palotie, Aarno; Pattie, Alison; van der Auwera, Sandra; Thalamuthu, Anbupalam; Knopman, David S; Rudan, Igor; Starr, John M; Wittfeld, Katharina; Kochan, Nicole A; Griswold, Michael E; Vitart, Veronique; Brodaty, Henry; Gottesman, Rebecca; Cox, Simon R; Psaty, Bruce M; Boerwinkle, Eric; Chasman, Daniel I; Grodstein, Francine.
Afiliação
  • Mei H; Department of Data Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS, USA. hmei@umc.edu.
  • Simino J; Gertrude C. Ford Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA. hmei@umc.edu.
  • Li L; Department of Data Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS, USA. jsimino@umc.edu.
  • Jiang F; Gertrude C. Ford Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA. jsimino@umc.edu.
  • Bis JC; Department of Biology, Tougaloo College, Jackson, MS, USA.
  • Davies G; Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Hill WD; Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
  • Xia C; Department of Psychology, Lothian Birth Cohorts Group, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Gudnason V; Department of Psychology, Lothian Birth Cohorts Group, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Yang Q; Department of Psychology, Lothian Birth Cohorts Group, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Lahti J; Icelandic Heart Association, Kopavogur, Iceland.
  • Smith JA; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Kirin M; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • De Jager P; The National Heart Lung and Blood Institute's Framingham Heart Study, Framingham, MA, USA.
  • Armstrong NJ; Turku Institute for Advanced Research, University of Turku, Turku, Finland.
  • Ghanbari M; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Kolcic I; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Moran C; Work completed while at The University of Edinburgh, Edinburgh, UK.
  • Teumer A; Taub Institute for Research On Alzheimer's Disease and the Aging Brain, Columbia Irving University Medical Center, New York, NY, USA.
  • Sargurupremraj M; Center for Translational and Computational Neuro-Immunology, Columbia University Medical Center, New York, NY, USA.
  • Mahmud S; Department of Neurology, Columbia University Medical Center, New York, NY, USA.
  • Fornage M; Mathematics and Statistics, Curtin University, Perth, Australia.
  • Zhao W; Department of Epidemiology, Erasmus Medical Center University Medical Center, Rotterdam, The Netherlands.
  • Satizabal CL; School of Medicine, University of Split, Split, Croatia.
  • Polasek O; Department of Geriatric Medicine, Frankston Hospital, Peninsula Health, Melbourne, Australia.
  • Räikkönen K; Peninsula Clinical School, Central Clinical School, Monash University, Melbourne, Australia.
  • Liewald DC; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
  • Homuth G; Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219, University of Bordeaux, Bordeaux, France.
  • Callisaya M; Department of Data Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS, USA.
  • Mather KA; The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Windham BG; Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA.
  • Zemunik T; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
  • Palotie A; The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
  • Pattie A; School of Medicine, University of Split, Split, Croatia.
  • van der Auwera S; Algebra University College, Ilica 242, Zagreb, Croatia.
  • Thalamuthu A; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Knopman DS; Department of Psychology, Lothian Birth Cohorts Group, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Rudan I; Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
  • Starr JM; Peninsula Clinical School, Central Clinical School, Monash University, Melbourne, Australia.
  • Wittfeld K; Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
  • Kochan NA; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
  • Griswold ME; Neuroscience Research Australia, Sydney, Australia.
  • Vitart V; Gertrude C. Ford Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA.
  • Brodaty H; Department of Medicine, Division of Geriatrics, School of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
  • Gottesman R; School of Medicine, University of Split, Split, Croatia.
  • Cox SR; Department of Medicine, Department of Neurology and Department of Psychiatry, Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Psaty BM; The Stanley Center for Psychiatric Research and Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Boerwinkle E; Department of Psychology, Lothian Birth Cohorts Group, University of Edinburgh, 7 George Square, Edinburgh, EH8 9JZ, UK.
  • Chasman DI; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
  • Grodstein F; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Alzheimers Res Ther ; 16(1): 14, 2024 01 20.
Article em En | MEDLINE | ID: mdl-38245754
ABSTRACT

BACKGROUND:

Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia.

METHODS:

We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes.

RESULTS:

The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues.

CONCLUSIONS:

VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Revista: Alzheimers Res Ther Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Estudo de Associação Genômica Ampla Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Aged / Humans Idioma: En Revista: Alzheimers Res Ther Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos