TY - JOUR
T1 - X‐chromosome-wide association study for Alzheimer’s disease
AU - EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE
AU - Le Borgne, Julie
AU - Gomez, Lissette
AU - Heikkinen, Sami
AU - Amin, Najaf
AU - Ahmad, Shahzad
AU - Choi, Seung Hoan
AU - Bis, Joshua
AU - Grenier-Boley, Benjamin
AU - Rodriguez, Omar Garcia
AU - Kleineidam, Luca
AU - Young, Juan
AU - Tripathi, Kumar Parijat
AU - Wang, Lily
AU - Varma, Achintya
AU - Campos-Martin, Rafael
AU - van der Lee, Sven
AU - Damotte, Vincent
AU - de Rojas, Itziar
AU - Palmal, Sagnik
AU - Lipton, Richard
AU - Reiman, Eric
AU - McKee, Ann
AU - De Jager, Philip
AU - Bush, William
AU - Small, Scott
AU - Levey, Allan
AU - Saykin, Andrew
AU - Foroud, Tatiana
AU - Albert, Marilyn
AU - Hyman, Bradley
AU - Petersen, Ronald
AU - Younkin, Steven
AU - Sano, Mary
AU - Wisniewski, Thomas
AU - Vassar, Robert
AU - Schneider, Julie
AU - Henderson, Victor
AU - Roberson, Erik
AU - DeCarli, Charles
AU - LaFerla, Frank
AU - Brewer, James
AU - Swerdlow, Russell
AU - Van Eldik, Linda
AU - Hamilton-Nelson, Kara
AU - Paulson, Henry
AU - Naj, Adam
AU - Lopez, Oscar
AU - Chui, Helena
AU - Seshadri, Sudha
AU - Ruiz, Agustín
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2025/6
Y1 - 2025/6
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85211480840
UR - https://www.scopus.com/pages/publications/85211480840#tab=citedBy
U2 - 10.1038/s41380-024-02838-5
DO - 10.1038/s41380-024-02838-5
M3 - Article
C2 - 39633006
AN - SCOPUS:85211480840
SN - 1359-4184
VL - 30
SP - 2335
EP - 2346
JO - Molecular psychiatry
JF - Molecular psychiatry
IS - 6
M1 - 113386
ER -