Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search

Stein, J. L., Hibar, D. P., Madsen, S. K., Khamis, M, McMahon, K. L., de Zubicaray, G. I., Hansell, N. K., Montgomery, G. W., Martin, N. G., Wright, M. J., Saykin, A. J., Jack Jr, C. R., Weiner. M. W., Toga. A. W., Thompson, P. M. and The Alzheimer’s Disease Neuroimaging Initiative (2011) Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search. Molecular Psychiatry, 16 9: 927-937. doi:10.1038/mp.2011.32


Author Stein, J. L.
Hibar, D. P.
Madsen, S. K.
Khamis, M
McMahon, K. L.
de Zubicaray, G. I.
Hansell, N. K.
Montgomery, G. W.
Martin, N. G.
Wright, M. J.
Saykin, A. J.
Jack Jr, C. R.
Weiner. M. W.
Toga. A. W.
Thompson, P. M.
The Alzheimer’s Disease Neuroimaging Initiative
Title Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search
Formatted title
Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
1476-5578
Publication date 2011-09
Sub-type Article (original research)
DOI 10.1038/mp.2011.32
Volume 16
Issue 9
Start page 927
End page 937
Total pages 11
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted abstract
The caudate is a subcortical brain structure implicated in many common neurological and psychiatric disorders. To identify specific genes associated with variations in caudate volume, structural magnetic resonance imaging and genome-wide genotypes were acquired from two large cohorts, the Alzheimer's Disease NeuroImaging Initiative (ADNI; N=734) and the Brisbane Adolescent/Young Adult Longitudinal Twin Study (BLTS; N=464). In a preliminary analysis of heritability, around 90% of the variation in caudate volume was due to genetic factors. We then conducted genome-wide association to find common variants that contribute to this relatively high heritability. Replicated genetic association was found for the right caudate volume at single-nucleotide polymorphism rs163030 in the ADNI discovery sample (P=2.36 × 10-6) and in the BLTS replication sample (P=0.012). This genetic variation accounted for 2.79 and 1.61% of the trait variance, respectively. The peak of association was found in and around two genes, WDR41 and PDE8B, involved in dopamine signaling and development. In addition, a previously identified mutation in PDE8B causes a rare autosomal-dominant type of striatal degeneration. Searching across both samples offers a rigorous way to screen for genes consistently influencing brain structure at different stages of life. Variants identified here may be relevant to common disorders affecting the caudate.
Keyword Caudate
Dopamine
Genome-wide association
Heritability
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Psychology Publications
Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 25 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 31 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Wed, 24 Aug 2011, 16:18:25 EST by Sandrine Ducrot on behalf of Centre for Advanced Imaging