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PMID: 22903471 Published · ppublish English 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.

Genome-wide association identifies genetic variants associated with lentiform nucleus volume in N = 1345 young and elderly subjects.

Brain imaging and behavior ·Vol. 7 ·No. 2 ·2013-06-00 ·Pages 102-15

Hibar DP, Stein JL, Ryles AB, Kohannim O, Jahanshad N, Medland SE, Hansell NK, McMahon KL, de Zubicaray GI, Montgomery GW, Martin NG, Wright MJ, Saykin AJ, Jack CR, Weiner MW, Toga AW, Thompson PM, Alzheimer’s Disease Neuroimaging Initiative

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.

MeSH Terms
Adult Aged Aged, 80 and over Alzheimer Disease/genetics,pathology Cognitive Dysfunction/genetics,pathology Corpus Striatum/pathology Female Genetic Predisposition to Disease/genetics Genetic Variation Genome-Wide Association Study Genotype Humans Longitudinal Studies Male Polymorphism, Single Nucleotide/genetics Young Adult
Authors & Affiliations
18 authors, click to expand affiliations / ORCID
Hibar Derrek P
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 Jason L
Ryles April B
Kohannim Omid
Jahanshad Neda
Medland Sarah E
Hansell Narelle K
McMahon Katie L
de Zubicaray Greig I
Montgomery Grant W
Martin Nicholas G
Wright Margaret J
Saykin Andrew J
Jack Clifford R
Weiner Michael W
Toga Arthur W
Thompson Paul M
Alzheimer’s Disease Neuroimaging Initiative
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Article Info
Journal
Brain imaging and behavior
Abbr.
Brain Imaging Behav
ISSN
1931-7565
DOI
10.1007/s11682-012-9199-7
Published
2013-06-00
Pages
102-15
Language
English
Region
United States
NLM ID
101300405
PMCID
PMC3779070
Subset
IM
Grants
NIA NIH HHS · K01 AG030514 · United States
NIA NIH HHS · R01 AG040060 · United States
NIBIB NIH HHS · EB01651 · United States
NIBIB NIH HHS · EB008432 · United States
NIA NIH HHS · R01 AG19771 · United States
NIA NIH HHS · F30AG041681 · United States
NLM NIH HHS · T15 LM07356 · United States
NIA NIH HHS · P30 AG010129 · United States
NIBIB NIH HHS · R01 EB008281 · United States
NLM NIH HHS · T15 LM007356 · United States
NIBIB NIH HHS · EB007813 · United States
NIBIB NIH HHS · R01 EB007813 · United States
NIA NIH HHS · R01 AG019771 · United States
NIA NIH HHS · AG016570 · United States
NIA NIH HHS · P30 AG10133 · United States
NIA NIH HHS · F30 AG041681 · United States
NIA NIH HHS · U24 AG021886 · United States
NIA NIH HHS · P30 AG010133 · United States
NIGMS NIH HHS · T32 GM008042 · United States
NCRR NIH HHS · R21 RR019771 · United States
NLM NIH HHS · R01 LM005639 · United States
NIA NIH HHS · U01 AG032984 · United States
NIA NIH HHS · U01 AG024904 · United States
NIA NIH HHS · U19 AG010483 · United States
NCRR NIH HHS · RR019771 · United States
NIA NIH HHS · P50 AG016570 · United States
NICHD NIH HHS · R01 HD050735 · United States
NIBIB NIH HHS · R01 EB008432 · United States
NIBIB NIH HHS · EB008281 · United States
NLM NIH HHS · LM05639 · United States
External Links
PubMed source DOI: 10.1007/s11682-012-9199-7 PMC Full Text View journal details
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