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Neuroimage. 2014 Aug 15;97:252-61. doi: 10.1016/j.neuroimage.2014.04.021. Epub 2014 Apr 13.

Common genetic variants and gene expression associated with white matter microstructure in the human brain.

Author information

1
Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT, USA; Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, 200 Retreat Avenue, CT, USA. Electronic address: emma.sprooten@yale.edu.
2
Department of Psychiatry, Yale University School of Medicine, 300 George Street, New Haven, CT, USA; Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital, 200 Retreat Avenue, CT, USA.
3
Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
4
Department of Psychiatry, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, USA.
5
Research Imaging Institute, University of Texas Health Science Center San Antonio, 8403 Floyd Curl Drive, San Antonio, TX, USA; South Texas Veterans Health System, 7400 Merton Minter, San Antonio, TX 78229, USA.
6
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Identifying genes that contribute to white matter microstructure should provide insights into the neurobiological processes that regulate white matter development, plasticity and pathology. We detected five significant SNPs using genome-wide association analysis on a global measure of fractional anisotropy in 776 individuals from large extended pedigrees. Genetic correlations and genome-wide association results indicated that the genetic signal was largely homogeneous across white matter regions. Using RNA transcripts derived from lymphocytes in the same individuals, we identified two genes (GNA13 and CCDC91) that are likely to be cis-regulated by top SNPs, and whose expression levels were also genetically correlated with fractional anisotropy. A transcript of HTR7 was phenotypically associated with FA, and was associated with an intronic genome-wide significant SNP. These results encourage further research in the mechanisms by which GNA13, HTR7 and CCDC91 influence brain structure, and emphasize a role for g-protein signaling in the development and maintenance of white matter microstructure in health and disease.

KEYWORDS:

Diffusion tensor imaging; Extended pedigrees; Gene expression; Genome-wide association; Transcripts; White matter

PMID:
24736177
PMCID:
PMC4107465
DOI:
10.1016/j.neuroimage.2014.04.021
[Indexed for MEDLINE]
Free PMC Article

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