Heritability of Magnetic Resonance Imaging (MRI) Traits in Alzheimer Disease Cases and Their Siblings in the MIRAGE Study
Abstract
Magnetic resonance imaging (MRI) traits can serve as more specific measures of degenerative or cerebrovascular brain injury than can be ascertained through personal history, risk factors, clinical signs, or symptoms. They are potentially useful intermediate phenotypes for genetic studies of Alzheimer disease (AD). Recent studies have estimated heritability of white matter hyperintensity (WMH) among cognitively normal family members to be between 0.55 and 0.73. Persons discordant for AD are expected to have substantially different MRI phenotype distributions; our goal was to determine whether MRI traits in siblings discordant for AD are heritable. We measured cerebral atrophy, medial temporal atrophy (MTA), WMH, and a rating of cerebrovascular disease (CVR) via MRI in 815 participants from 424 families of the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study. Residual heritability after adjustment for covariates ranged from 0.17 (P=0.009) for MTA to 0.57 (P=10(-7)) for CVR. The number of APOE-epsilon4 alleles was significantly associated with WMH (P=0.01) and CVR (P=0.005) but not cerebral atrophy (P=0.25) or MTA (P=0.83). Heritability remained significant and high after adjusting for APOE genotype, suggesting that a substantial proportion of the additive genetic variation in these MRI traits is explained by other genes. In the Multi-Institutional Research in Alzheimer's Genetic Epidemiology Study of AD-discordant siblings, MRI traits are heritable and are potential endophenotypes for genetic association studies.
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Structure-based endophenotypes are heritable.
“are heritable [223, 224]”
From Genetic architecture of Alzheimer's disease (2020) · cites this paper as [224]
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- Authors
- Lunetta, K. L., Erlich, P. M., T.Cuenco, K., Adrienne Cupples, L., Green, R. C., Farrer, L. A., & DeCarli, C.
- Affiliations
- Boston University (US)
- University of California, Davis (US)
- Corresponding author
- Lunetta, Kathryn L.
- Venue
- Alzheimer Disease & Associated Disorders
- Published
- 2007-04
- Volume
- 21
- Issue
- 2
- Pages
- 85-91
- ISSN
- 0893-0341 (ISSN-L)
- OpenAlex
- W2055957121
- Cited by
- 34
- References
- 9
- Citations by year
- 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2015: 1 · 2013: 3 · 2012: 2
- FWCI
- 3.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer Disease & Associated Disorders (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01-HG/AG-02213, P30AG013846, R01AG009029, R01 AG09029, P30-AG13846))
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- Alzheimer's disease, heritability, white matter hyperintensities, medial temporal lobe atrophy, brain atrophy, cerebrovascular disease, APOE ε4, endophenotypes, genetic epidemiology
- MeSH terms
- Alzheimer Disease, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Pedigree, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Siblings, Apolipoprotein E4
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