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

Emma Sprooten, Emma E. Knowles, D. Reese McKay, Harald HH Goring, Joanne E Curran, Jack W. Kent, Melanie A Carless, Thomas D. Dyer, Eugene I. Drigalenko, Rene L. Olvera, Peter T. Fox, Laura A Almasy, Ravindranath Duggirala, Peter Kochunov, John C Blangero, David C. Glahn

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)252-261
Number of pages10
StatePublished - Aug 15 2014


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

ASJC Scopus subject areas

  • Neurology
  • Cognitive Neuroscience


Dive into the research topics of 'Common genetic variants and gene expression associated with white matter microstructure in the human brain'. Together they form a unique fingerprint.

Cite this