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

Title: X‐chromosome-wide association study for Alzheimer’s disease
Authors: Le Borgne, Julie; Gomez, Lissette; Heikkinen, Sami; Amin, Najaf; Ahmad, Shahzad; Choi, Seung Hoan; Bis, Joshua; Grenier-Boley, Benjamin; Rodriguez, Omar Garcia; Kleineidam, Luca; Bellenguez, Céline; EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE
Contributors: Le Borgne, Julie; Gomez, Lissette; Heikkinen, Sami; Amin, Najaf; Ahmad, Shahzad; Choi, Seung Hoan; Bis, Joshua; Grenier-Boley, Benjamin; Rodriguez, Omar Garcia; Kleineidam, Luca; Bellenguez, Céline; EADB, GR@ACE, DEGESCO, EADI, GERAD, DemGene, FinnGen, ADGC, CHARGE
Publication Year: 2024
Collection: Georg-August-Universität Göttingen: GoeScholar
Description: 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.
Document Type: article in journal/newspaper
Language: English
Relation: 2838
DOI: 10.1038/s41380-024-02838-5
Availability: https://resolver.sub.uni-goettingen.de/purl?gro-2/147121; https://doi.org/10.1038/s41380-024-02838-5
Rights: info:eu-repo/semantics/openAccess ; https://creativecommons.org/licenses/by/4.0
Accession Number: edsbas.787670DF
Database: BASE