Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) 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, C. R., Weiner, M. W., Toga, A. W., & Thompson, P. M. (2011) Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N1198) using genome-wide search. Molecular Psychiatry, 16(9), pp. 927-937.
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.
Impact and interest:
Citation counts are sourced monthly from and citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from theindexing service can be viewed at the linked Google Scholar™ search.
|Item Type:||Journal Article|
|Keywords:||Caudate, dopamine, genome-wide association, heritability, PDE8B, WDR41|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Owner:||Copyright 2011 Macmillan Publishers Limited|
|Deposited On:||04 Sep 2015 01:15|
|Last Modified:||04 Sep 2015 01:15|
Repository Staff Only: item control page