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Investigating the genetics of hippocampal volume in older adults without dementia.
Mather, Karen A; Armstrong, Nicola J; Wen, Wei; Kwok, John B; Assareh, Amelia A; Thalamuthu, Anbupalam; Reppermund, Simone; Duesing, Konsta; Wright, Margaret J; Ames, David; Trollor, Julian N; Brodaty, Henry; Schofield, Peter R; Sachdev, Perminder S.
Afiliação
  • Mather KA; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
  • Armstrong NJ; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, Australia; School of Mathematics and Statistics, UNSW, Sydney, Australia.
  • Wen W; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
  • Kwok JB; Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, UNSW, Sydney, Australia.
  • Assareh AA; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
  • Thalamuthu A; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
  • Reppermund S; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia.
  • Duesing K; The Commonwealth Scientific and Industrial Research Organisation (CSIRO) Animal Food and Health Sciences Division, Sydney, Australia.
  • Wright MJ; QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Ames D; National Ageing Research Institute, Royal Melbourne Hospital, Melbourne, Australia; Academic Unit for Psychiatry of Old Age, University of Melbourne, Melbourne, Australia.
  • Trollor JN; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia; Department of Developmental Disability Neuropsychiatry, UNSW, Sydney, Australia.
  • Brodaty H; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia; Primary Dementia Collaborative Research Centre, UNSW, Sydney, Australia.
  • Schofield PR; Neuroscience Research Australia, Sydney, Australia; School of Medical Sciences, UNSW, Sydney, Australia.
  • Sachdev PS; Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales (UNSW), Sydney, Australia; Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, Australia.
PLoS One ; 10(1): e0116920, 2015.
Article em En | MEDLINE | ID: mdl-25625606
ABSTRACT
Hippocampal atrophy is observed with ageing and age-related neurodegenerative disease. Identification of the genetic correlates of hippocampal volume (HV) and atrophy may assist in elucidating the mechanisms of ageing and age-related neurodegeneration. Using two community cohorts of older Caucasians we estimated the heritability of HV and examined associations of HV with previously identified single nucleotide polymorphisms (SNPs). In addition we undertook genome-association studies (GWAS) examining HV and HV atrophy. Participants were community-dwelling non-demented older adults from the longitudinal Sydney Memory and Ageing Study (Sydney MAS) (N = 498) and the Older Australian Twins Study (OATS) (N = 351) aged 65 and over. HV was measured using T1-weighted magnetic resonance images. Heritability of HV was estimated in OATS. Genome-wide genotyping was imputed using the 1K Genomes reference set. Associations with HV-candidate and Alzheimer's disease (AD)-related SNPs were investigated. A GWAS examining HV (in both cohorts) and an exploratory GWAS of HV atrophy over two years (in Sydney MAS only) were also undertaken. HV heritability was estimated at 62-65%. The previously identified GWAS HV SNP (rs6581612) and the candidate BDNF SNP (rs6265) were nominally significant (p = 0.047 and p = 0.041 respectively). No AD-related SNPs, including the APOE ε4 polymorphism, were significant. No significant results were observed for either of the GWAS undertaken. Despite our estimate of a high heritability of HV, our results are consistent with a highly polygenic model suggesting that SNPs identified from prior studies, including GWAS meta-analyses, can be difficult to replicate in smaller samples of older adults.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hipocampo Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: PLoS One Ano de publicação: 2015 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hipocampo Limite: Aged / Aged80 / Female / Humans / Male Idioma: En Revista: PLoS One Ano de publicação: 2015 Tipo de documento: Article