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Genomic Studies Across the Lifespan Point to Early Mechanisms Determining Subcortical Volumes.
Le Grand, Quentin; Satizabal, Claudia L; Sargurupremraj, Muralidharan; Mishra, Aniket; Soumaré, Aicha; Laurent, Alexandre; Crivello, Fabrice; Tsuchida, Ami; Shin, Jean; Macalli, Mélissa; Singh, Baljeet; Beiser, Alexa S; DeCarli, Charles; Fletcher, Evan; Paus, Tomas; Lathrop, Mark; Adams, Hieab H H; Bis, Joshua C; Seshadri, Sudha; Tzourio, Christophe; Mazoyer, Bernard; Debette, Stéphanie.
Afiliación
  • Le Grand Q; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France.
  • Satizabal CL; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas; Department of Population Health Sciences, UT Health San Antonio, San Antonio, Texas; Framingham Heart Study, Framingham, Massachusetts; Department of Neurology, Boston University School o
  • Sargurupremraj M; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas.
  • Mishra A; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France.
  • Soumaré A; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France.
  • Laurent A; University of Bordeaux, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CNRS, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CEA, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional i
  • Crivello F; University of Bordeaux, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CNRS, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CEA, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional i
  • Tsuchida A; University of Bordeaux, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CNRS, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CEA, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional i
  • Shin J; Department of Physiology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada; Department of Nutritional Sciences, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
  • Macalli M; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France.
  • Singh B; Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California Davis, Davis, California.
  • Beiser AS; Framingham Heart Study, Framingham, Massachusetts; Department of Neurology, Boston University School of Medicine, Boston, Massachusetts; Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
  • DeCarli C; Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California Davis, Davis, California.
  • Fletcher E; Imaging of Dementia and Aging Laboratory, Department of Neurology, University of California Davis, Davis, California.
  • Paus T; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, Centre Hospitalier Universitaire Sainte-Justine, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada.
  • Lathrop M; McGill Genome Center, McGill University, Montreal, Quebec, Canada.
  • Adams HHH; Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands; Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, the Netherlands.
  • Bis JC; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington.
  • Seshadri S; Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, Texas; Department of Population Health Sciences, UT Health San Antonio, San Antonio, Texas; Framingham Heart Study, Framingham, Massachusetts; Department of Neurology, Boston University School o
  • Tzourio C; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France; Bordeaux University Hospital, Department of Medical Informatics, Bordeaux, France.
  • Mazoyer B; University of Bordeaux, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CNRS, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional imaging group, Bordeaux, France; CEA, Institute of Neurodegenerative Diseases, UMR5293, Neurofunctional i
  • Debette S; University of Bordeaux, INSERM, Bordeaux Population Health Center, UMR1219, Bordeaux, France; Bordeaux University Hospital, Department of Neurology, Institute of Neurodegenerative Diseases, Bordeaux, France. Electronic address: stephanie.debette@u-bordeaux.fr.
Biol Psychiatry Cogn Neurosci Neuroimaging ; 7(6): 616-628, 2022 06.
Article en En | MEDLINE | ID: mdl-34700051
BACKGROUND: Subcortical brain structures play a key role in pathological processes of age-related neurodegenerative disorders. Mounting evidence also suggests that early-life factors may have an impact on the development of common late-life neurological diseases, including genetic factors that can influence both brain maturation and neurodegeneration. METHODS: Using large population-based brain imaging datasets across the lifespan (N ≤ 40,628), we aimed to 1) estimate the heritability of subcortical volumes in young (18-35 years), middle (35-65 years), and older (65+ years) age, and their genetic correlation across age groups; 2) identify whether genetic loci associated with subcortical volumes in older persons also show associations in early adulthood, and explore underlying genes using transcriptome-wide association studies; and 3) explore their association with neurological phenotypes. RESULTS: Heritability of subcortical volumes consistently decreased with increasing age. Genetic risk scores for smaller caudate nucleus, putamen, and hippocampus volume in older adults were associated with smaller volumes in young adults. Individually, 10 loci associated with subcortical volumes in older adults also showed associations in young adults. Within these loci, transcriptome-wide association studies showed that expression of several genes in brain tissues (especially MYLK2 and TUFM) was associated with subcortical volumes in both age groups. One risk variant for smaller caudate nucleus volume (TUFM locus) was associated with lower cognitive performance. Genetically predicted Alzheimer's disease was associated with smaller subcortical volumes in middle and older age. CONCLUSIONS: Our findings provide novel insights into the genetic determinants of subcortical volumes across the lifespan. More studies are needed to decipher the underlying biology and clinical impact.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Longevidad Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Humans Idioma: En Revista: Biol Psychiatry Cogn Neurosci Neuroimaging Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Imagen por Resonancia Magnética / Longevidad Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Humans Idioma: En Revista: Biol Psychiatry Cogn Neurosci Neuroimaging Año: 2022 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos