Contributions of rare and common variation to early-onset and atypical dementia risk
- Carter A. Wright1,2,
- Jared W. Taylor1,
- Meagan Cochran1,
- James M.J. Lawlor1,
- Belle A. Moyers1,
- Michelle D. Amaral1,
- Zachary T. Bonnstetter1,
- Princess Carter3,
- Veronika Solomon3,
- Richard M. Myers1,
- Marissa Natelson Love3,
- David S. Geldmacher3,
- Sara J. Cooper1,
- Erik D. Roberson3 and
- J. Nicholas Cochran1,3
- 1HudsonAlpha Institute for Biotechnology, Huntsville, Alabama 35806, USA;
- 2University of Alabama in Huntsville, Huntsville, Alabama 35899, USA;
- 3Alzheimer's Disease Center, Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
- Corresponding author: ncochran{at}hudsonalpha.org; eroberson{at}uabmc.edu
Abstract
We collected and analyzed genomic sequencing data from individuals with clinician-diagnosed early-onset or atypical dementia. Thirty-two patients were previously described, with 68 newly described in this report. Of those 68, 62 patients self-reported white, non-Hispanic ethnicity and 6 reported as African–American, non-Hispanic. Fifty-three percent of patients had a returnable variant. Five patients harbored a pathogenic variant as defined by the American College of Medical Genetics criteria for pathogenicity. A polygenic risk score (PRS) was calculated for Alzheimer's patients in the total cohort and compared to the scores of a late-onset Alzheimer's cohort and a control set. Patients with early-onset Alzheimer's had higher non-APOE PRSs than patients with late-onset Alzheimer's, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk.
Footnotes
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[Supplemental material is available for this article.]
- Received January 31, 2023.
- Accepted June 7, 2023.
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