Age at Onset in Two Common Neurodegenerative Diseases Is Genetically Controlled
Open accessAbstract
To identify genes influencing age at onset (AAO) in two common neurodegenerative diseases, a genomic screen was performed for AAO in families with Alzheimer disease (AD; n=449) and Parkinson disease (PD; n=174). Heritabilities between 40%--60% were found in both the AD and PD data sets. For PD, significant evidence for linkage to AAO was found on chromosome 1p (LOD = 3.41). For AD, the AAO effect of APOE (LOD = 3.28) was confirmed. In addition, evidence for AAO linkage on chromosomes 6 and 10 was identified independently in both the AD and PD data sets. Subsequent unified analyses of these regions identified a single peak on chromosome 10q between D10S1239 and D10S1237, with a maximum LOD score of 2.62. These data suggest that a common gene affects AAO in these two common complex neurodegenerative diseases.
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Age at onset of Alzheimer's disease is highly heritable in both familial and sporadic forms, with predicted genetic contributions up to 78% in sporadic late-onset AD and over 90% in monogenic early-onset familial AD.
“AAO of AD is highly heritable in both familial and sporadic forms of the disease, with predicted genetic contributions of up to 78% in the sporadic late-onset form,3, 4 and over 90% in a monogenic early-onset familial form.5”
From Whole-genome sequencing suggests a chemokine gene cluster that modifies age at onset in familial Alzheimer's disease (2015) · cites this paper as [3]
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Self-citation
- Authors
- Li, Y.-J., Scott, W. K., Hedges, D. J., Zhang, F., Gaskell, P. C., Nance, M. A., Watts, R. L., Hubble, J. P., Koller, W. C., Pahwa, R., Stern, M. B., Hiner, B. C., Jankovic, J., Allen, F. H., Goetz, C. G., Mastaglia, F., Stajich, J. M., Gibson, R. A., Middleton, L. T., Saunders, A. M., Scott, B. L., Small, G. W., Nicodemus, K. K., Reed, A. D., Schmechel, D. E., Welsh-Bohmer, K. A., Conneally, P. M., Roses, A. D., Gilbert, J. R., Vance, J. M., Haines, J. L., & Pericak-Vance, M. A.
- Affiliations
- Duke University (US)
- Emory University (US)
- The Ohio State University (US)
- University of Miami (US)
- University of Kansas Medical Center (US)
- University of Pennsylvania Health System (US)
- Marshfield Clinic (US)
- Baylor College of Medicine (US)
- Rush University Medical Center (US)
- The University of Western Australia (AU)
- GlaxoSmithKline (United Kingdom) (GB)
- University of California, Los Angeles (US)
- Vanderbilt University Medical Center (US)
- Indiana University (US)
- GlaxoSmithKline (United States) (US)
- ORCID
- Li, Yi-Ju
- Scott, William K.
- Zhang, Fengyu
- Nance, Martha A.
- Pahwa, Rajesh
- Jankovic, Joseph
- Goetz, Christopher G.
- Mastaglia, Frank
- Gibson, Rachel A.
- Middleton, Lefkos T.
- Saunders, Ann M.
- Scott, Burton L.
- Small, Gary W.
- Nicodemus, Kristin K.
- Welsh-Bohmer, Kathleen A.
- Gilbert, John R.
- Vance, Jeffery M.
- Haines, Jonathan L.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2002-04
- Volume
- 70
- Issue
- 4
- Pages
- 985-993
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC379130
- OpenAlex
- W2129494556
- Cited by
- 312
- References
- 43
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 5 · 2022: 2 · 2021: 3 · 2020: 3 · 2019: 6 · 2018: 3 · 2017: 10 · 2016: 11 · 2015: 9 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 21.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Murdoch University Research Portal (submittedVersion)
- Funders
- Vanderbilt University Medical Center
- National Institutes of Health
- National Institute on Aging (AG-11268, P50 AG05128, AG-13308, AG 10123, P50AG005128, R01AG013308, P60AG011268, P30AG010123, U24AG021886)
- National Institute of Mental Health (MH52453, R01MH052453)
- National Institute of Neurological Disorders and Stroke (P01NS026630, NS31 153, P01-NS-26630, P50 NS39764, R01NS031153, P50NS039764)
- National Center for Research Resources ((M01 RR00865), M01RR000865)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- age of onset, Alzheimer's disease, Parkinson's disease, neurodegenerative diseases, genetic linkage, heritability, apolipoprotein E, chromosome 1p, chromosome 10q, familial disease, complex disease genetics
- MeSH terms
- Aged, Alzheimer Disease, Apolipoproteins E, Chromosome Mapping, Chromosomes, Human, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 10, Chromosomes, Human, Pair 6, Humans, Lod Score, Middle Aged, Models, Genetic, Parkinson Disease, Age of Onset, Genetic Predisposition to Disease, Multifactorial Inheritance
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