Journal Article

DZNE-2025-00631

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png X-chromosome-wide association study for Alzheimer's disease.

Le Borgne, J. ; Gomez, L. ; Heikkinen, S. ; Amin, N. ; Ahmad, S. ; Choi, S. H. ; Bis, J. ; Grenier-Boley, B. ; Rodriguez, O. G. ; Kleineidam, L.DZNE* ; Young, J. ; Tripathi, K. P. ; Wang, L. ; Varma, A. ; Campos-Martin, R. ; van der Lee, S. ; Damotte, V. ; de Rojas, I. ; Palmal, S. ; EADB, G. (Collaboration Author) ; Lipton, R. ; Reiman, E. ; McKee, A. ; De Jager, P. ; Bush, W. ; Small, S. ; Levey, A. ; Saykin, A. ; Foroud, T. ; Albert, M. ; Hyman, B. ; Petersen, R. ; Younkin, S. ; Sano, M. ; Wisniewski, T. ; Vassar, R. ; Schneider, J. ; Henderson, V. ; Roberson, E. ; DeCarli, C. ; LaFerla, F. ; Brewer, J. ; Swerdlow, R. ; Van Eldik, L. ; Hamilton-Nelson, K. ; Paulson, H. ; Naj, A. ; Lopez, O. ; Chui, H. ; Crane, P. ; Grabowski, T. ; Kukull, W. ; Asthana, S. ; Craft, S. ; Strittmatter, S. ; Cruchaga, C. ; Leverenz, J. ; Goate, A. ; Kamboh, M. I. ; George-Hyslop, P. S. ; Valladares, O. ; Kuzma, A. ; Cantwell, L. ; Riemenschneider, M. ; Morris, J. ; Slifer, S. ; Dalmasso, C. ; Castillo, A. ; Küçükali, F. ; Peters, O.DZNE* ; Schneider, A.DZNE* ; Dichgans, M.DZNE* ; Rujescu, D. ; Scherbaum, N. ; Deckert, J. ; Riedel-Heller, S. ; Hausner, L. ; Molina-Porcel, L. ; Düzel, E.DZNE* ; Grimmer, T. ; Wiltfang, J.DZNE* ; Heilmann-Heimbach, S. ; Moebus, S. ; Tegos, T. ; Scarmeas, N. ; Dols-Icardo, O. ; Moreno, F. ; Pérez-Tur, J. ; Bullido, M. J. ; Pastor, P. ; Sánchez-Valle, R. ; Álvarez, V. ; Boada, M. ; García-González, P. ; Puerta, R. ; Mir, P. ; Real, L. M. ; Piñol-Ripoll, G. ; García-Alberca, J. M. ; Royo, J. L. ; Rodriguez-Rodriguez, E. ; Soininen, H. ; de Mendonça, A. ; Mehrabian, S. ; Traykov, L. ; Hort, J. ; Vyhnalek, M. ; Thomassen, J. Q. ; Pijnenburg, Y. A. L. ; Holstege, H. ; van Swieten, J. ; Ramakers, I. ; Verhey, F. ; Scheltens, P. ; Graff, C. ; Papenberg, G. ; Giedraitis, V. ; Boland, A. ; Deleuze, J.-F. ; Nicolas, G. ; Dufouil, C. ; Pasquier, F. ; Hanon, O. ; Debette, S. ; Grünblatt, E. ; Popp, J. ; Ghidoni, R. ; Galimberti, D. ; Arosio, B. ; Mecocci, P. ; Solfrizzi, V. ; Parnetti, L. ; Squassina, A. ; Tremolizzo, L. ; Borroni, B. ; Nacmias, B. ; Spallazzi, M. ; Seripa, D. ; Rainero, I. ; Daniele, A. ; Bossù, P. ; Masullo, C. ; Rossi, G. ; Jessen, F.DZNE* ; Fernandez, V. ; Kehoe, P. G. ; Frikke-Schmidt, R. ; Tsolaki, M. ; Sánchez-Juan, P. ; Sleegers, K. ; Ingelsson, M. ; Haines, J. ; Farrer, L. ; Mayeux, R. ; Wang, L.-S. ; Sims, R. ; DeStefano, A. ; Schellenberg, G. D. ; Seshadri, S. ; Amouyel, P. ; Williams, J. ; van der Flier, W. ; Ramirez, A.DZNE* ; Pericak-Vance, M. ; Andreassen, O. A. ; Van Duijn, C. ; Hiltunen, M. ; Ruiz, A. ; Dupuis, J. ; Martin, E. ; Lambert, J.-C. ; Kunkle, B. ; Bellenguez, C.

2025
Springer Nature [London]

This record in other databases:    

Please use a persistent id in citations: doi:10.1038/s41380-024-02838-5

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 × 10-8) 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.

Keyword(s): Humans (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Genome-Wide Association Study: methods (MeSH) ; Female (MeSH) ; Chromosomes, Human, X: genetics (MeSH) ; Male (MeSH) ; Genetic Predisposition to Disease: genetics (MeSH) ; Polymorphism, Single Nucleotide: genetics (MeSH) ; Aged (MeSH) ; X Chromosome Inactivation: genetics (MeSH) ; Aged, 80 and over (MeSH) ; Case-Control Studies (MeSH)

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Contributing Institute(s):

1. Neuropsychology (AG Wagner)
2. Biomarker-Assisted Early Detection of Dementias (AG Peters)
3. Translational Dementia Research (Bonn) (AG Schneider)
4. Vascular Cognitive Impairment & Post-Stroke Dementia (AG Dichgans)
5. Clinical Neurophysiology and Memory (AG Düzel)
6. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)
7. Clinical Alzheimer’s Disease Research (AG Jessen)
8. Patient Studies (Bonn) (Patient Studies (Bonn))

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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