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
22903411
TITLE
DISCOVERY OF GENES THAT AFFECT HUMAN BRAIN CONNECTIVITY: A GENOME-WIDE ANALYSIS OF THE CONNECTOME.
ABSTRACT
Human brain connectivity is disrupted in a wide range of disorders - from Alzheimer's disease to autism - but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70?70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.
DATE PUBLISHED
2012
HISTORY
PUBSTATUS PUBSTATUSDATE
entrez 2012/08/21 06:00
pubmed 2012/08/21 06:00
medline 2012/08/21 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Jahanshad N Jahanshad Neda N Laboratory of Neuro Imaging, Department of Neurology, UCLA School of Medicine, Los Angeles, CA.
Hibar DP Hibar Derrek P DP
Ryles A Ryles April A
Toga AW Toga Arthur W AW
McMahon KL McMahon Katie L KL
de Zubicaray GI de Zubicaray Greig I GI
Hansell NK Hansell Narelle K NK
Montgomery GW Montgomery Grant W GW
Martin NG Martin Nicholas G NG
Wright MJ Wright Margaret J MJ
Thompson PM Thompson Paul M PM
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Proceedings / IEEE International Symposium on Biomedical Imaging: from nano to macro. IEEE International Symposium on Biomedical Imaging
ISOABBREVIATION: Proc IEEE Int Symp Biomed Imaging
YEAR: 2012
MONTH:
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Print
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MEDLINE JOURNAL
MEDLINETA: Proc IEEE Int Symp Biomed Imaging
COUNTRY: United States
ISSNLINKING: 1945-7928
NLMUNIQUEID: 101492570
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
P41 RR013642 NCRR NIH HHS United States
R01 AG040060 NIA NIH HHS United States
R01 EB008281 NIBIB NIH HHS United States
R01 HD050735 NICHD NIH HHS United States
T15 LM007356 NLM NIH HHS United States
GENERAL NOTE
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