Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease

S. J. Furney, A. Simmons, G. Breen, I. Pedroso, K. Lunnon, P. Proitsi, A. Hodges, J. Powell, L. O. Wahlund, I. Kloszewska, P. Mecocci, H. Soininen, M. Tsolaki, B. Vellas, C. Spenger, M. Lathrop, Li Shen, S. Kim, Andrew Saykin, M. W. WeinerS. Lovestone

Research output: Contribution to journalArticle

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Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with considerable evidence suggesting an initiation of disease in the entorhinal cortex and hippocampus and spreading thereafter to the rest of the brain. In this study, we combine genetics and imaging data obtained from the Alzheimer's Disease Neuroimaging Initiative and the AddNeuroMed study. To identify genetic susceptibility loci for AD, we conducted a genome-wide study of atrophy in regions associated with neurodegeneration in this condition. We identified one single-nucleotide polymorphism (SNP) with a disease-specific effect associated with entorhinal cortical volume in an intron of the ZNF292 gene (rs1925690; P-value=2.6 × 10 -8; corrected P-value for equivalent number of independent quantitative traits=7.7 × 10 -8) and an intergenic SNP, flanking the ARPP-21 gene, with an overall effect on entorhinal cortical thickness (rs11129640; P-value=5.6 × 10 -8; corrected P-value=1.7 × 10 -7). Gene-wide scoring also highlighted PICALM as the most significant gene associated with entorhinal cortical thickness (P-value=6.7 × 10 -6).

Original languageEnglish
Pages (from-to)1130-1138
Number of pages9
JournalMolecular Psychiatry
Volume16
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Quantitative Trait Loci
Atrophy
Alzheimer Disease
Genome
Genes
Single Nucleotide Polymorphism
Entorhinal Cortex
Genetic Loci
Genetic Predisposition to Disease
Neuroimaging
Neurodegenerative Diseases
Introns
Hippocampus
Brain

Keywords

  • Alzheimer's disease
  • imaging-genetics
  • quantitative trait

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

Cite this

Furney, S. J., Simmons, A., Breen, G., Pedroso, I., Lunnon, K., Proitsi, P., ... Lovestone, S. (2011). Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. Molecular Psychiatry, 16(11), 1130-1138. https://doi.org/10.1038/mp.2010.123

Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. / Furney, S. J.; Simmons, A.; Breen, G.; Pedroso, I.; Lunnon, K.; Proitsi, P.; Hodges, A.; Powell, J.; Wahlund, L. O.; Kloszewska, I.; Mecocci, P.; Soininen, H.; Tsolaki, M.; Vellas, B.; Spenger, C.; Lathrop, M.; Shen, Li; Kim, S.; Saykin, Andrew; Weiner, M. W.; Lovestone, S.

In: Molecular Psychiatry, Vol. 16, No. 11, 11.2011, p. 1130-1138.

Research output: Contribution to journalArticle

Furney, SJ, Simmons, A, Breen, G, Pedroso, I, Lunnon, K, Proitsi, P, Hodges, A, Powell, J, Wahlund, LO, Kloszewska, I, Mecocci, P, Soininen, H, Tsolaki, M, Vellas, B, Spenger, C, Lathrop, M, Shen, L, Kim, S, Saykin, A, Weiner, MW & Lovestone, S 2011, 'Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease', Molecular Psychiatry, vol. 16, no. 11, pp. 1130-1138. https://doi.org/10.1038/mp.2010.123
Furney, S. J. ; Simmons, A. ; Breen, G. ; Pedroso, I. ; Lunnon, K. ; Proitsi, P. ; Hodges, A. ; Powell, J. ; Wahlund, L. O. ; Kloszewska, I. ; Mecocci, P. ; Soininen, H. ; Tsolaki, M. ; Vellas, B. ; Spenger, C. ; Lathrop, M. ; Shen, Li ; Kim, S. ; Saykin, Andrew ; Weiner, M. W. ; Lovestone, S. / Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease. In: Molecular Psychiatry. 2011 ; Vol. 16, No. 11. pp. 1130-1138.
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