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
22888310
TITLE
Discovery and Replication of Gene Influences on Brain Structure Using LASSO Regression.
ABSTRACT
We implemented least absolute shrinkage and selection operator (LASSO) regression to evaluate gene effects in genome-wide association studies (GWAS) of brain images, using an MRI-derived temporal lobe volume measure from 729 subjects scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sparse groups of SNPs in individual genes were selected by LASSO, which identifies efficient sets of variants influencing the data. These SNPs were considered jointly when assessing their association with neuroimaging measures. We discovered 22 genes that passed genome-wide significance for influencing temporal lobe volume. This was a substantially greater number of significant genes compared to those found with standard, univariate GWAS. These top genes are all expressed in the brain and include genes previously related to brain function or neuropsychiatric disorders such as MACROD2, SORCS2, GRIN2B, MAGI2, NPAS3, CLSTN2, GABRG3, NRXN3, PRKAG2, GAS7, RBFOX1, ADARB2, CHD4, and CDH13. The top genes we identified with this method also displayed significant and widespread post hoc effects on voxelwise, tensor-based morphometry (TBM) maps of the temporal lobes. The most significantly associated gene was an autism susceptibility gene known as MACROD2. We were able to successfully replicate the effect of the MACROD2 gene in an independent cohort of 564 young, Australian healthy adult twins and siblings scanned with MRI (mean age: 23.8 ± 2.2 SD years). Our approach powerfully complements univariate techniques in detecting influences of genes on the living brain.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2012/03/12
accepted 2012/07/12
epublish 2012/08/06
entrez 2012/08/14 06:00
pubmed 2012/08/14 06:00
medline 2012/08/14 06:01
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Kohannim O Kohannim Omid O Imaging Genetics Center at the Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine Los Angeles, CA, USA.
Hibar DP Hibar Derrek P DP
Stein JL Stein Jason L JL
Jahanshad N Jahanshad Neda N
Hua X Hua Xue X
Rajagopalan P Rajagopalan Priya P
Toga AW Toga Arthur W AW
Jack CR Jr Jack Clifford R CR
Weiner MW Weiner Michael W MW
de Zubicaray GI de Zubicaray Greig I GI
McMahon KL McMahon Katie L KL
Hansell NK Hansell Narelle K NK
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Thompson PM Thompson Paul M PM
Alzheimer’s Disease Neuroimaging Initiative
INVESTIGATORS
JOURNAL
VOLUME: 6
ISSUE:
TITLE: Frontiers in neuroscience
ISOABBREVIATION: Front Neurosci
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1662-453X
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Front Neurosci
COUNTRY: Switzerland
ISSNLINKING: 1662-453X
NLMUNIQUEID: 101478481
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
F30 AG041681 NIA NIH HHS United States
K01 AG030514 NIA NIH HHS United States
P30 AG010129 NIA NIH HHS United States
P50 AG016570 NIA NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 MH097268 NIMH NIH HHS United States
R21 EB001561 NIBIB NIH HHS United States
R21 RR019771 NCRR NIH HHS United States
T32 GM008042 NIGMS NIH HHS United States
U01 AG024904 NIA NIH HHS United States
U24 AG021886 NIA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
GWAS
LASSO
MACROD2
MRI
imaging genetics
neuroimaging
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
PMC3412288 NLM