X Chromosome Genetic Risk Across Sex, APOE*4, and Pleiotropic Traits Reveals Novel Alzheimer's Disease Mechanisms and Risk Genes
This study provides novel insights into biological mechanisms that contribute to X-linked genetic risk for AD in an APOE*4 and sex-specific manner, identifying various novel risk loci. Notably, 29 female-biased risk loci were uncovered, which may shed light on sex disparities in AD. Overall, our findings will aid in elucidating AD pathways and drug targets relevant to personalized medicine.
Authors
- Yann Le Guen (ORCID: https://orcid.org/0000-0001-6649-8364)
- Victoria C. Merritt (ORCID: https://orcid.org/0000-0001-5683-4168)
- R. L. Hauger
- Timothy J. Hohman (ORCID: https://orcid.org/0000-0002-3377-7014)
- the VA Million Veteran Program
- Derek B. Archer (ORCID: https://orcid.org/0000-0001-8638-0785)
- Logan C. Dumitrescu (ORCID: https://orcid.org/0000-0002-9782-9944)
- Danielle Marie Reid (ORCID: https://orcid.org/0000-0002-3316-9115)
- Beth C. Mormino
- Karly Alex Cody (ORCID: https://orcid.org/0000-0001-5996-2560)
- Valerio Napolioni (ORCID: https://orcid.org/0000-0002-4378-6838)
- Michael D. Greicius (ORCID: https://orcid.org/0000-0002-5462-9037)
- Michaël E. Belloy (ORCID: https://orcid.org/0000-0001-7748-9033)
- Mary Ellen I. Koran
- Richard Sherva
- Matthew S. Panizzon
- Ting‐Chen Wang
- Rui Zhang
- Noah Cook
- Mark W. Logue
- Chenyu Yang
- FinnGen
- J. Michael Gaziano
Institutions
- Boston University (US)
- Università di Camerino (IT)
- Brigham and Women's Hospital (US)
- Vanderbilt University (US)
- Washington University in St. Louis (US)
- VA Boston Healthcare System (US)
- University of California San Diego (US)
- VA San Diego Healthcare System (US)
- National Center for PTSD (US)
- Mayo Clinic Hospital (US)
- Vanderbilt University Medical Center (US)
- Stanford University (US)
Publication Details
- Journal
- Alzheimer s & Dementia
- Published
- 2025-12-01
- DOI
- https://doi.org/10.1002/alz70855_098765
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00