Imaging-wide association study: integrating imaging endophenotypes in GWAS
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A new and powerful approach, called imaging-wide association study (IWAS), is proposed to integrate imaging endophenotypes with GWAS to boost statistical power and enhance biological interpretation for GWAS discoveries. IWAS extends the promising transcriptome-wide association study (TWAS) from using gene expression endophenotypes to using imaging and other endophenotypes with a much wider range of possible applications. As illustration, we use gray-matter volumes of several brain regions of interest (ROIs) drawn from the ADNI-1 structural MRI data as imaging endophenotypes, which are then applied to the individual-level GWAS data of ADNI-GO/2 and a large meta-analyzed GWAS summary statistics dataset (based on about 74,000 individuals), uncovering some novel genes significantly associated with Alzheimer's disease (AD). We also compare the performance of IWAS with TWAS, showing much larger numbers of significant AD-associated genes discovered by IWAS, presumably due to the stronger link between brain atrophy and AD than that between gene expression of normal individuals and the risk for AD. The proposed IWAS is general and can be applied to other imaging endophenotypes, and GWAS individual-level or summary association data.
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Integrating multiple imaging traits provides further improved diagnostic classification.
“Groups are actively working to integrate multiple imaging traits together, providing an even further improved diagnostic classification [232, 233]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [232]
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Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“Groups are actively working to integrate multiple imaging traits together, providing an even further improved diagnostic classification (Xu et al., 2017; Scelsi et al., 2018) which will likely advance our understanding of brain-wide pathologies that occur in AD.”
BackgroundKang, M., Ang, T. F. A., Devine, S. A., Sherva, R., Mukherjee, S., Trittschuh, E. H., Gibbons, L. E., Scollard, P., Lee, M., Choi, S.-E., et al. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00633-4 · Cited by 29 · see citing works
- Authors
- Xu, Z., Wu, C., & Pan, W.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Pan, Wei
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2017-10
- Volume
- 159
- Pages
- 159-169
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC5671364
- OpenAlex
- W2736837914
- Cited by
- 56
- References
- 55
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 1 · 2023: 13 · 2022: 6 · 2021: 13 · 2020: 8 · 2019: 6 · 2018: 1 · 2017: 1
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 301 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- NeuroImage (acceptedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Biomedical Imaging and Bioengineering
- Biogen Idec
- BioClinica
- Servier
- Synarc
- Genentech
- Alzheimer's Disease Neuroimaging Initiative
- University of Southern California
- Merck
- U.S. Department of Defense (W81XWH-12-2-0012)
- Roche
- GE Healthcare
- University of California, San Diego
- National Institute on Aging
- Takeda Pharmaceuticals North America
- Novartis Pharmaceuticals Corporation
- Eisai
- Foundation for the National Institutes of Health
- Fujirebio US
- National Institutes of Health (U01 AG024904)
- Pfizer
- Northern California Institute for Research and Education
- Eli Lilly and Company
- Alzheimer's Association
- Bristol-Myers Squibb
- Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- transcriptome-wide association study, gray matter volume, Alzheimer's disease, brain atrophy, risk genes, statistical power, ADNI
- MeSH terms
- Alzheimer Disease, Genotype, Humans, Genome-Wide Association Study, Endophenotypes
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