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Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group
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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/).
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“However, the CST ROI from the JHU WMPM atlas is limited to a small region in the inferior portion of the brain and has been shown to be the least reliable and reproducible ROI (Jahanshad et al., 2013; Acheson et al., 2017)”
From Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3 (2019) · cites this paper as Jahanshad et al., 2013
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“Although many large-scale multi-site DTI studies have obtained consistent results even when acquisition protocols across sites are not harmonized in advance (Jahanshad et al., 2013; Kochunov et al., 2014; Acheson et al., 2017; Kelly et al., 2018), differences in dMRI acquisition parameters, including vendor, voxel size, and angular resolution, are known to affect derived dMRI measures (Alexander”
From Diffusion MRI Indices and Their Relation to Cognitive Impairment in Brain Aging: The Updated Multi-protocol Approach in ADNI3 (2019) · cites this paper as Jahanshad et al., 2013
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Metadata
- Authors
- Jahanshad, N., Kochunov, P. V., Sprooten, E., Mandl, R. C., Nichols, T. E., Almasy, L., Blangero, J., Brouwer, R. M., Curran, J. E., de Zubicaray, G. I., Duggirala, R., Fox, P. T., Hong, L. E., Landman, B. A., Martin, N. G., McMahon, K. L., Medland, S. E., Mitchell, B. D., Olvera, R. L., Peterson, C. P., Starr, J. M., Sussmann, J. E., Toga, A. W., Wardlaw, J. M., Wright, M. J., Hulshoff Pol, H. E., Bastin, M. E., McIntosh, A. M., Deary, I. J., Thompson, P. M., & Glahn, D. C.
- Affiliations
- University of California, Los Angeles (US)
- University of Maryland, Baltimore (US)
- Royal Edinburgh Hospital (GB)
- Utrecht University (NL)
- University of Warwick (GB)
- Texas Biomedical Research Institute (US)
- The University of Queensland (AU)
- The University of Texas at San Antonio Health Science Center (US)
- Vanderbilt University (US)
- QIMR Berghofer Medical Research Institute (AU)
- University of Edinburgh (GB)
- Yale University (US)
- ORCID
- Jahanshad, Neda
- Kochunov, Peter V.
- Sprooten, Emma
- Mandl, René C.
- Nichols, Thomas E.
- Almasy, Laura
- Blangero, John
- Brouwer, Rachel M.
- Curran, Joanne E.
- de Zubicaray, Greig I.
- Fox, Peter T.
- Hong, L. Elliot
- Landman, Bennett A.
- Martin, Nicholas G.
- McMahon, Katie L.
- Medland, Sarah E.
- Mitchell, Braxton D.
- Olvera, Rene L.
- Starr, John M.
- Toga, Arthur W.
- Wardlaw, Joanna M.
- Wright, Margaret J.
- Bastin, Mark E.
- McIntosh, Andrew M.
- Deary, Ian J.
- Thompson, Paul M.
- Glahn, David C.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 81
- Pages
- 455-469
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3729717
- OpenAlex
- W2118347577
- Cited by
- 393
- References
- 86
- Citations by year
- 2026: 15 · 2025: 22 · 2024: 28 · 2023: 20 · 2022: 21 · 2021: 32 · 2020: 45 · 2019: 38 · 2018: 31 · 2017: 32 · 2016: 32 · 2015: 32 · 2014: 28 · 2013: 16
- FWCI
- 27.94
- Type
- journal article
- Language
- en
- Update notices
- erratum (2014-04-15)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- PubMed Central (acceptedVersion)
- QUT ePrints (Queensland University of Technology) (submittedVersion, cc-by-nc-nd)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
- Faculty of Health; Institute of Health and Biomedical Innovation
- Funders
- R01 HD050735 (486682)
- R01 EB015611 (EB008432, EB008281, EB007813)
- MH0708143 (FT0991634)
- MH083824 (087727/Z/08/Z)
- MH078111
- MH59490
- National Health and Medical Research Council (NHMRC
- NIH (EB015611-01, U54MH091657-03)
- ARC Future Fellowship
- Wellcome Trust
- NARSAD Independent Investigator Award
- Scottish Funding Council Senior Clinical Fellowship
- Academy of Medical Sciences/Health Foundation Clinician Scientist Fellowship
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Keywords
- diffusion tensor imaging, fractional anisotropy, heritability, white matter integrity, ENIGMA consortium, mega-analysis
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Brain, Brain Mapping, Female, Humans, Image Processing, Computer-Assisted, Male, Middle Aged, Pilot Projects, Registries, Anisotropy, Young Adult, Diffusion Tensor Imaging
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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