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. and Sachdev, Perminder S. (2015) Investigating the genetics of hippocampal volume in older adults without dementia. PLoS ONE, 10 1: . doi:10.1371/journal.pone.0116920

Author 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.
Title Investigating the genetics of hippocampal volume in older adults without dementia
Journal name PLoS ONE   Check publisher's open access policy
ISSN 1932-6203
Publication date 2015-01-27
Sub-type Article (original research)
DOI 10.1371/journal.pone.0116920
Open Access Status DOI
Volume 10
Issue 1
Total pages 12
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2016
Language eng
Formatted 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.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
Queensland Brain Institute Publications
School of Psychology Publications
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Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
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