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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
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
Cites Nat Genet. 2012 May;44(5):545-51 22504421
Cites Nat Genet. 2012 May;44(5):552-61 22504417
Cites Arch Gen Psychiatry. 1999 Mar;56(3):254-60 10078503
Cites Drug Metab Dispos. 2000 Sep;28(9):1107-11 10950857
Cites Trends Neurosci. 2000 Oct;23(10 Suppl):S8-19 11052215
Cites Biol Psychiatry. 2000 Oct 15;48(8):830-43 11063978
Cites Neurol Clin. 2000 Nov;18(4):789-806 11072261
Cites Pediatr Res. 2002 Feb;51(2):236-43 11809920
Cites Mol Pharmacol. 2002 Aug;62(2):320-5 12130684
Cites Drug Metab Dispos. 2002 Oct;30(10):1043-52 12228178
Cites Neuron. 2002 Oct 10;36(2):241-63 12383780
Cites Hum Brain Mapp. 2002 Nov;17(3):143-55 12391568
Cites Nat Rev Neurosci. 2003 Jan;4(1):37-48 12511860
Cites AJNR Am J Neuroradiol. 2003 Oct;24(9):1849-56 14561615
Cites Drug Metab Dispos. 2004 Nov;32(11):1201-8 15304429
Cites Neuroimage. 2004 Oct;23(2):724-38 15488422
Cites Neuroimage. 2004;23 Suppl 1:S208-19 15501092
Cites Br J Psychol. 1970 Aug;61(3):303-21 5457503
Cites Adv Neurol. 1983;39:865-81 6229162
Cites Neurology. 1986 Aug;36(8):1042-7 3526177
Cites Proc Natl Acad Sci U S A. 1988 Aug;85(15):5733-7 2456581
Cites Psychopharmacology (Berl). 1989;97(3):309-18 2497479
Cites Brain. 1991 Aug;114 ( Pt 4):1953-75 1832073
Cites Am J Psychiatry. 1994 May;151(5):752-5 7909412
Cites Science. 1994 Sep 30;265(5181):2037-48 8091226
Cites Brain Res. 1995 Feb 20;672(1-2):276-80 7749747
Cites Arch Gen Psychiatry. 1996 Jul;53(7):607-16 8660127
Cites Neuropsychopharmacology. 1996 Aug;15(2):133-42 8840349
Cites Chem Biol Interact. 1997 Aug 29;106(1):29-45 9305407
Cites Pharmacol Ther. 2005 Jun;106(3):357-87 15922018
Cites Mol Psychiatry. 2005 Jul;10(7):678-85 15724142
Cites Expert Opin Drug Metab Toxicol. 2006 Feb;2(1):41-9 16863467
Cites J Pharmacol Exp Ther. 2007 Jan;320(1):266-73 17050781
Cites Hum Brain Mapp. 2007 Jun;28(6):464-73 17415783
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Am J Hum Genet. 2007 Nov;81(5):913-26 17924335
Cites J Nutr Biochem. 2008 Feb;19(2):129-37 18061429
Cites Nat Rev Genet. 2008 May;9(5):356-69 18398418
Cites Drug Metab Rev. 2008;40(2):263-301 18464046
Cites BMC Psychiatry. 2008;8:51 18590567
Cites Am J Psychiatry. 2008 Aug;165(8):1015-23 18381902
Cites Arch Gen Psychiatry. 2008 Sep;65(9):1017-32 18762588
Cites Psychiatry Res. 2009 Jun 30;172(3):210-4 19303260
Cites Brain. 2009 Aug;132(Pt 8):1997-2001 19634211
Cites Br J Psychiatry. 2009 Sep;195(3):194-201 19721106
Cites Neuroimage. 2010 Jan 15;49(2):1213-23 19786105
Cites Neuroimage. 2010 Jun;51(2):542-54 20197096
Cites Nature. 2010 Jun 24;465(7301):1033-8 20577206
Cites J Psychiatr Res. 2010 Sep;44(12):748-53 20185149
Cites Hum Brain Mapp. 2010 Nov;31(11):1751-62 20162602
Cites Genet Epidemiol. 2010 Dec;34(8):816-34 21058334
Cites PLoS One. 2010;5(12):e14480 21217833
Cites Am J Hum Genet. 2011 Mar 11;88(3):283-93 21397060
Cites Neuroimage. 2011 Jun 1;56(3):907-22 21352927
Cites Am J Hum Genet. 2011 May 13;88(5):586-98 21565292
Cites Proc Natl Acad Sci U S A. 2011 May 17;108(20):8345-50 21531904
Cites Science. 2012 Mar 30;335(6076):1634-6 22461613
Cites J Neurosci. 2012 Jun 20;32(25):8732-45 22723713
GRANTS
GRANTID AGENCY COUNTRY
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
F30 AG041681 NIA NIH HHS United States
F30AG041681 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
K01 AG030514 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 AG010133 NIA NIH HHS United States
P30 AG10133 NIA NIH HHS United States
P50 AG016570 NIA NIH HHS United States
R01 AG019771 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 AG19771 NIA NIH HHS United States
R01 EB007813 NIBIB NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 EB008432 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
R01 LM005639 NLM NIH HHS United States
R21 RR019771 NCRR NIH HHS United States
RR019771 NCRR NIH HHS United States
T15 LM007356 NLM NIH HHS United States
T15 LM07356 NLM NIH HHS United States
T32 GM008042 NIGMS NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U01 AG032984 NIA NIH HHS United States
U01 AG032984 NIA NIH HHS United States
U24 AG021886 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Aged
Aged, 80 and over
Alzheimer Disease 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
Mild Cognitive Impairment pathology
Polymorphism, Single Nucleotide genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS439314 NLM
PMC3779070 NLM