X‐chromosome-wide association study for Alzheimer’s disease

Journal article

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer’s Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10−8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10−6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Authors: Le Borgne, J; Gomez, L; Heikkinen, S; Amin, N; Ahmad, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer Nature [academic journals on nature.com]
• Journal: Molecular Psychiatry
• Volume: 30
• Issue: 6
• Pages: 2335-2346
• Publication date: 2024-12-04
• Acceptance date: 2024-11-07
• DOI: 10.1038/s41380-024-02838-5
• EISSN: 1476-5578
• ISSN: 1359-4184
• Language: English