Contributions of rare and common variation to early-onset and atypical dementia risk
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 sixty-eight newly described in this report. Of those sixty-eight, sixty-two patients reported Caucasian, non-Hispanic ethnicity and six 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 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-APOEpolygenic risk scores than patients with late onset Alzheimer’s, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wright, Carter A. [VerfasserIn] |
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| doi: |
10.1101/2023.02.06.23285383 |
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| PPN (Katalog-ID): |
XBI03863791X |
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| 520 | |a 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 sixty-eight newly described in this report. Of those sixty-eight, sixty-two patients reported Caucasian, non-Hispanic ethnicity and six 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 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-APOEpolygenic risk scores than patients with late onset Alzheimer’s, supporting the conclusion that both rare and common genetic variation associate with early-onset neurodegenerative disease risk. | ||
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| 700 | 1 | |a Taylor, Jared W. |e verfasserin |4 aut | |
| 700 | 1 | |a Cochran, Meagan |e verfasserin |0 (orcid)0000-0002-9852-5504 |4 aut | |
| 700 | 1 | |a Lawlor, James M.J. |e verfasserin |4 aut | |
| 700 | 1 | |a Moyers, Belle A. |e verfasserin |4 aut | |
| 700 | 1 | |a Amaral, Michelle D. |e verfasserin |4 aut | |
| 700 | 1 | |a Bonnstetter, Zachary T. |e verfasserin |4 aut | |
| 700 | 1 | |a Carter, Princess |e verfasserin |4 aut | |
| 700 | 1 | |a Solomon, Veronika |e verfasserin |4 aut | |
| 700 | 1 | |a Myers, Richard M. |e verfasserin |4 aut | |
| 700 | 1 | |a Love, Marissa Natelson |e verfasserin |4 aut | |
| 700 | 1 | |a Geldmacher, David S. |e verfasserin |4 aut | |
| 700 | 1 | |a Cooper, Sara J. |e verfasserin |4 aut | |
| 700 | 1 | |a Roberson, Erik D. |e verfasserin |4 aut | |
| 700 | 1 | |a Cochran, J. Nicholas |e verfasserin |4 aut | |
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