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
22903471
TITLE
Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N?=?1345 young and elderly subjects.
ABSTRACT
Deficits in lentiform nucleus volume and morphometry are implicated in a number of genetically influenced disorders, including Parkinson's disease, schizophrenia, and ADHD. Here we performed genome-wide searches to discover common genetic variants associated with differences in lentiform nucleus volume in human populations. We assessed structural MRI scans of the brain in two large genotyped samples: the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 706) and the Queensland Twin Imaging Study (QTIM; N = 639). Statistics of association from each cohort were combined meta-analytically using a fixed-effects model to boost power and to reduce the prevalence of false positive findings. We identified a number of associations in and around the flavin-containing monooxygenase (FMO) gene cluster. The most highly associated SNP, rs1795240, was located in the FMO3 gene; after meta-analysis, it showed genome-wide significant evidence of association with lentiform nucleus volume (P MA  = 4.79 × 10(-8)). This commonly-carried genetic variant accounted for 2.68 % and 0.84 % of the trait variability in the ADNI and QTIM samples, respectively, even though the QTIM sample was on average 50 years younger. Pathway enrichment analysis revealed significant contributions of this gene to the cytochrome P450 pathway, which is involved in metabolizing numerous therapeutic drugs for pain, seizures, mania, depression, anxiety, and psychosis. The genetic variants we identified provide replicated, genome-wide significant evidence for the FMO gene cluster's involvement in lentiform nucleus volume differences in human populations.
DATE PUBLISHED
2013 Jun
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/08/21 06:00
pubmed 2012/08/21 06:00
medline 2013/12/18 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Hibar DP Hibar Derrek P DP Imaging Genetics Center at the Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Neuroscience Research Building 225E 635 Charles Young Drive, Los Angeles, CA, 90095-1769, USA.
Stein JL Stein Jason L JL
Ryles AB Ryles April B AB
Kohannim O Kohannim Omid O
Jahanshad N Jahanshad Neda N
Medland SE Medland Sarah E SE
Hansell NK Hansell Narelle K NK
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Saykin AJ Saykin Andrew J AJ
Jack CR Jr Jack Clifford R CR
Weiner MW Weiner Michael W MW
Toga AW Toga Arthur W AW
Thompson PM Thompson Paul M PM
Alzheimer’s Disease Neuroimaging Initiative
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 2
TITLE: Brain imaging and behavior
ISOABBREVIATION: Brain Imaging Behav
YEAR: 2013
MONTH: Jun
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1931-7565
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Brain Imaging Behav
COUNTRY: United States
ISSNLINKING: 1931-7557
NLMUNIQUEID: 101300405
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTID AGENCY COUNTRY
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Alzheimer Disease pathology
Cognitive Dysfunction pathology
Corpus Striatum pathology
Female pathology
Genetic Predisposition to Disease genetics
Genetic Variation genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Longitudinal Studies genetics
Male genetics
Polymorphism, Single Nucleotide genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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