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Power Estimates for Voxel-Based Genetic Association Studies Using Diffusion Imaging

  • Neda Jahanshad
  • Peter Kochunov
  • David C. Glahn
  • John Blangero
  • Thomas E. Nichols
  • Katie L. McMahon
  • Greig I. de Zubicaray
  • Nicholas G. Martin
  • Margaret J. Wright
  • Clifford R. JackJr.
  • Matt A. Bernstein
  • Michael W. Weiner
  • Arthur W. Toga
  • Paul M. Thompson
Conference paper
Part of the Mathematics and Visualization book series (MATHVISUAL)

Abstract

The quest to discover genetic variants that affect the human brain will be accelerated by screening brain images from large populations. Even so, the wealth of information in medical images is often reduced to a single numeric summary, such as a regional volume or an average signal, which is then analyzed in a genome wide association study (GWAS). The high cost and penalty for multiple comparisons often constrains us from searching over the entire image space. Here, we developed a method to compute and boost power to detect genetic associations in brain images. We computed voxel-wise heritability estimates for fractional anisotropy in over 1,100 DTI scans, and used the results to threshold FA images from new studies. We describe voxel selection criteria to optimally boost power, as a function of the sample size and allele frequency cut-off. We illustrate our methods by analyzing publicly-available data from the ADNI2 project.

Keywords

Neuroimaging genetics Heritability GWAS DTI Multiple comparisons correction 

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Neda Jahanshad
    • 1
    • 2
  • Peter Kochunov
    • 3
  • David C. Glahn
    • 4
  • John Blangero
    • 5
  • Thomas E. Nichols
    • 6
    • 7
  • Katie L. McMahon
    • 8
  • Greig I. de Zubicaray
    • 9
  • Nicholas G. Martin
    • 10
  • Margaret J. Wright
    • 10
  • Clifford R. JackJr.
    • 11
  • Matt A. Bernstein
    • 11
  • Michael W. Weiner
    • 12
    • 13
  • Arthur W. Toga
    • 1
  • Paul M. Thompson
    • 1
    • 2
  1. 1.Imaging Genetics Center, Institute of Neuroimaging and Informatics, Keck School of MedicineUSCLos AngelesUSA
  2. 2.Department of NeurologySchool of Medicine, UCLALos AngelesUSA
  3. 3.Maryland Psychiatric Research Center, U of MarylandBaltimoreUSA
  4. 4.Olin Neuropsychiatry Research CenterYale School of MedicineNew HavenUSA
  5. 5.Department of GeneticsTexas Biomedical Research InstituteSan AntonioUSA
  6. 6.Department of Statistics & Warwick Manufacturing GroupU of WarwickCoventryUK
  7. 7.Oxford Centre for Functional MRI of the Brain (FMRIB)Oxford UniversityOxfordUK
  8. 8.Centre for Advanced ImagingUniversity of QueenslandBrisbaneAustralia
  9. 9.School of PsychologyUniversity of QueenslandBrisbaneAustralia
  10. 10.Queensland Institute of Medical ResearchBrisbaneAustralia
  11. 11.Department of RadiologyMayo ClinicRochesterUSA
  12. 12.Department of Radiology, Medicine, and PsychiatryUC San FranciscoSan FranciscoUSA
  13. 13.Department of Veterans Affairs Medical CenterSan FranciscoUSA

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