title: Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group.
abstract: The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors: Neda
authors: N
authors: Jahanshad
authors: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Peter V
authors: PV
authors: Kochunov
authors: Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA; Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
authors: Emma
authors: E
authors: Sprooten
authors: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: René C
authors: RC
authors: Mandl
authors: Department of Statistics & Warwick Manufacturing Group, The University of Warwick, Coventry, UK; Oxford Centre for Functional MRI of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, Oxford University, UK.
authors: Thomas E
authors: TE
authors: Nichols
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Laura
authors: L
authors: Almasy
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: John
authors: J
authors: Blangero
authors: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Rachel M
authors: RM
authors: Brouwer
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Joanne E
authors: JE
authors: Curran
authors: University of Queensland, School of Psychology, Brisbane, Australia.
authors: Greig I
authors: GI
authors: de Zubicaray
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Ravi
authors: R
authors: Duggirala
authors: Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA; South Texas Veterans Administration Medical Center, San Antonio, TX, USA.
authors: Peter T
authors: PT
authors: Fox
authors: Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: L Elliot
authors: LE
authors: Hong
authors: Vanderbilt University, Electrical Engineering, Nashville, TN, USA.
authors: Bennett A
authors: BA
authors: Landman
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: University of Queensland, Center for Advanced Imaging, Brisbane, Australia.
authors: Katie L
authors: KL
authors: McMahon
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Sarah E
authors: SE
authors: Medland
authors: Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Braxton D
authors: BD
authors: Mitchell
authors: Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
authors: Rene L
authors: RL
authors: Olvera
authors: Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
authors: Charles P
authors: CP
authors: Peterson
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors: John M
authors: JM
authors: Starr
authors: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
authors: Jessika E
authors: JE
authors: Sussmann
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
authors: Arthur W
authors: AW
authors: Toga
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Brain Research Imaging Centre, Division of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
authors: Joanna M
authors: JM
authors: Wardlaw
authors: Queensland Institute of Medical Research, Brisbane, Australia.
authors: Margaret J
authors: MJ
authors: Wright
authors: Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Hilleke E
authors: HE
authors: Hulshoff Pol
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Brain Research Imaging Centre, Division of Neuroimaging Sciences, University of Edinburgh, Edinburgh, UK.
authors: Mark E
authors: ME
authors: Bastin
authors: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
authors: Andrew M
authors: AM
authors: McIntosh
authors: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
authors: Ian J
authors: IJ
authors: Deary
authors: Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA. Electronic address: thompson@loni.ucla.edu.
authors: Paul M
authors: PM
authors: Thompson
authors: Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA.
authors: David C
authors: DC
authors: Glahn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001921:Brain; D001931:Brain Mapping; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012042:Registries; D055815:Young Adult
keywords: Diffusion Tensor Imaging (DTI); Heritability; Imaging genetics; Meta-analysis; Multi-site; Reliability
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