X-chromosome-wide association study for Alzheimer's disease.
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| Abstract | 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) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10). 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. |
| Year of Publication | 2024
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| Journal | Molecular psychiatry
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| Date Published | 12/2024
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| ISSN | 1476-5578
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| DOI | 10.1038/s41380-024-02838-5
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| PubMed ID | 39633006
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