Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21502949
TITLE
Discovery and replication of dopamine-related gene effects on caudate volume in young and elderly populations (N=1198) using genome-wide search.
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.
DATE PUBLISHED
2011 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/04/19
entrez 2011/04/20 06:00
pubmed 2011/04/20 06:00
medline 2012/01/18 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Stein JL Stein J L JL Department of Neurology, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
Hibar DP Hibar D P DP
Madsen SK Madsen S K SK
Khamis M Khamis M M
McMahon KL McMahon K L KL
de Zubicaray GI de Zubicaray G I GI
Hansell NK Hansell N K NK
Montgomery GW Montgomery G W GW
Martin NG Martin N G NG
Wright MJ Wright M J MJ
Saykin AJ Saykin A J AJ
Jack CR Jr Jack C R CR
Weiner MW Weiner M W MW
Toga AW Toga A W AW
Thompson PM Thompson P M PM
Alzheimer’s Disease Neuroimaging Initiative Investigators
INVESTIGATORS
JOURNAL
VOLUME: 16
ISSUE: 9
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2011
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Comparative Study
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
1F31MH087061 NIMH NIH HHS United States
AG016570 NIA NIH HHS United States
EB007813 NIBIB NIH HHS United States
EB008281 NIBIB NIH HHS United States
EB008432 NIBIB NIH HHS United States
EB01651 NIBIB NIH HHS United States
F31 MH087061 NIMH NIH HHS United States
F31 MH087061-02 NIMH NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K01 AG030514-04 NIA NIH HHS United States
LM05639 NLM NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P30 AG010129-13 NIA NIH HHS United States
P50 AG016570 NIA NIH HHS United States
P50 AG016570-07 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB007813-04 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008281-14 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 EB008432-03 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735-04 NICHD NIH HHS United States
R01 LM005639 NLM NIH HHS United States
R01 LM005639-10 NLM NIH HHS United States
R21 RR019771 NCRR NIH HHS United States
R21 RR019771-02 NCRR NIH HHS United States
RR019771 NCRR NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG024904-07 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
3',5'-Cyclic-AMP Phosphodiesterases genetics
Adult genetics
Age Factors genetics
Aged genetics
Caudate Nucleus anatomy & histology
Dopamine genetics
Female genetics
Genetic Variation genetics
Genome-Wide Association Study statistics & numerical data
Genotype statistics & numerical data
Heredity genetics
Humans genetics
Magnetic Resonance Imaging methods
Male methods
Neuroimaging statistics & numerical data
Polymorphism, Single Nucleotide statistics & numerical data
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
EC 3.1.4.17 3',5'-Cyclic-AMP Phosphodiesterases
EC 3.1.4.17 PDE8B protein, human
VTD58H1Z2X Dopamine
OTHER ID's
OTHERID SOURCE
NIHMS274387 NLM
PMC3140560 NLM
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