Common variant genetic background risk impacts Alzheimer's disease rare genetic variant associations
Stratifying individuals into those with lower and higher risk for AD based on aggregated effects of common variants enhanced the detection of RV and LV associations. Our results suggest that a PRS calculated from common variants may not necessarily correspond to an individual's genetic relative risk for AD. These findings also provide unique opportunities to study RVs whose effects are opposite to the risk conferred by the genetic background.
Authors
- Congcong Zhu (ORCID: https://orcid.org/0000-0002-0143-7453)
- Xiaoling Zhang (ORCID: https://orcid.org/0000-0001-8237-1857)
- Zainab Khurshid (ORCID: https://orcid.org/0000-0002-5857-5443)
- William S. Bush (ORCID: https://orcid.org/0000-0002-9729-6519)
- Oluwatosin A Olayinka
- John J. Farrell (ORCID: https://orcid.org/0000-0001-6502-1572)
- Eden R. Martin (ORCID: https://orcid.org/0000-0002-4035-9152)
- Kathryn L. Lunetta (ORCID: https://orcid.org/0000-0002-9268-810X)
- Lindsay AA. Farrer
- Gerald D. Schellenberg
- Li‐San Wang
- The Alzheimer's Disease Sequencing Project (ADSP)
- Margaret Pericak‐Vance
- Jonathan L Haines
Institutions
- Boston University (US)
- Boston Medical Center (US)
- University of Miami (US)
- New World School of the Arts (US)
- Framingham Heart Study (US)
- Dr. John T. Macdonald Foundation (US)
- Institute on Aging (US)
- Boston Public Schools (US)
- Case Western Reserve University (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70855_106998
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00