title: Common genetic variants and gene expression associated with white matter microstructure in the human brain.
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.
authors.affiliation: 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.
authors.forename: Emma
authors.initials: E
authors.lastname: Sprooten
authors.affiliation: 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.
authors.forename: Emma E
authors.initials: EE
authors.lastname: Knowles
authors.affiliation: 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.
authors.forename: D Reese
authors.initials: DR
authors.lastname: McKay
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Harald H
authors.initials: HH
authors.lastname: Göring
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Joanne E
authors.initials: JE
authors.lastname: Curran
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Jack W
authors.initials: JW
authors.lastname: Kent
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Carless
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Dyer
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Drigalenko
authors.affiliation: Department of Psychiatry, University of Texas Health Science Center San Antonio, 7703 Floyd Curl Drive, San Antonio, TX, USA.
authors.forename: Rene L
authors.initials: RL
authors.lastname: Olvera
authors.affiliation: 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.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Fox
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Almasy
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Duggirala
authors.affiliation: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kochunov
authors.affiliation: Department of Genetics, Texas Biomedical Research Institute, PO Box 760549, San Antonio, TX, USA.
authors.forename: John
authors.initials: J
authors.lastname: Blangero
authors.affiliation: 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.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
mesh_terms: D016880:Anisotropy; D015331:Cohort Studies; D056324:Diffusion Tensor Imaging; D015870:Gene Expression / Q000502:physiology*; D014644:Genetic Variation / Q000502:physiology*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D017058:Mexican Americans; D020641:Polymorphism, Single Nucleotide; D066127:White Matter / Q000033:anatomy & histology* / Q000648:ultrastructure*
keywords: Diffusion tensor imaging; Extended pedigrees; Gene expression; Genome-wide association; Transcripts; White matter
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