期刊
MOLECULAR PSYCHIATRY
卷 16, 期 9, 页码 927-937出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/mp.2011.32
关键词
caudate; dopamine; genome-wide association; heritability; PDE8B; WDR41
资金
- Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health) [U01 AG024904]
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
- NIH [P30 AG010129, K01 AG030514]
- Dana Foundation
- NIA
- NIBIB
- NICHD
- National Library of Medicine
- National Center for Research Resources [AG016570, EB01651, LM05639, RR019771, EB008432, EB008281, EB007813]
- National Institute of Child Health and Human Development [R01 HD050735]
- National Health and Medical Research Council (NHMRC), Australia [486682]
- ARCS foundation
- NIMH [1F31MH087061]
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 X 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. Molecular Psychiatry (2011) 16, 927-937; doi:10.1038/mp.2011.32; published online 19 April 2011
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