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Neuroimage. 2013 Nov 1;81:455-469. doi: 10.1016/j.neuroimage.2013.04.061. Epub 2013 Apr 28.

Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group.

Author information

1
Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA.
2
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD, USA.
3
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.
4
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, The Netherlands.
5
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.
6
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
7
University of Queensland, School of Psychology, Brisbane, Australia.
8
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.
9
Vanderbilt University, Electrical Engineering, Nashville, TN, USA.
10
Queensland Institute of Medical Research, Brisbane, Australia.
11
University of Queensland, Center for Advanced Imaging, Brisbane, Australia.
12
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
13
Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.
14
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
15
Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
16
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.
17
Imaging Genetics Center, Laboratory of Neuro Imaging, UCLA School of Medicine, Los Angeles, CA, USA. Electronic address: thompson@loni.ucla.edu.
18
Olin Neuropsychiatry Research Center in the Institute of Living, Yale University School of Medicine, New Haven, CT, USA.

Erratum in

  • Neuroimage. 2014 Apr 15;90:470-1.

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/).

KEYWORDS:

Diffusion Tensor Imaging (DTI); Heritability; Imaging genetics; Meta-analysis; Multi-site; Reliability

PMID:
23629049
PMCID:
PMC3729717
DOI:
10.1016/j.neuroimage.2013.04.061
[Indexed for MEDLINE]
Free PMC Article

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