02414nas a2200253   4500008004100000245006200041210005600103260000800159520173400167100001901901700001701920700001601937700001301953700001501966700001401981700001601995700002102011700001902032700002002051700001402071700001802085700002102103856003602124       2024                        eng d00a{The Role of X Chromosome in Alzheimer's Disease Genetics0 aRole of X Chromosome in Alzheimers Disease Genetics  cApr3 aThe X chromosome has remained enigmatic in Alzheimer's disease (AD), yet it makes up 5% of the genome and carries a high proportion of genes expressed in the brain, making it particularly appealing as a potential source of unexplored genetic variation in AD.\ Perform the first large-scale X chromosome-wide association study (XWAS) of AD. Primary analyses are non-stratified, while secondary analyses evaluate sex-stratified effects.\ Meta-analysis of genetic association studies in case-control, family-based, population-based, and longitudinal AD-related cohorts from the US Alzheimer's Disease Genetics Consortium (ADGC) and Alzheimer's Disease Sequencing Project (ADSP), the UK Biobank (UKB), the Finnish health registry (FinnGen), and the US Million Veterans Program (MVP). Risk for AD evaluated through case-control logistic regression analyses. Data were analyzed between January 2023 and March 2024.\ Genetic data available from high-density single-nucleotide polymorphism (SNP) microarrays and whole-genome sequencing (WGS). Summary statistics for multi-tissue expression and protein quantitative trait loci (QTL) available from published studies, enabling follow-up genetic colocalization analyses.\ 1,629,863 eligible participants were selected from referred and volunteer samples, of which 477,596 were excluded for analysis exclusion criteria. Number of participants who declined to participate in original studies was not available.\ 5e-8) significance.\ genes.\ regulates pH homeostasis in Golgi secretory compartments and is anticipated to have downstream effects on amyloid beta accumulation. Overall, this study significantly advances our knowledge of AD genetics and may provide novel biological drug targets.1 aBelloy, M., E.1 aGuen, Y., L.1 aStewart, I.1 aHerz, J.1 aSherva, R.1 aZhang, R.1 aMerritt, V.1 aPanizzon, M., S.1 aHauger, R., L.1 aGaziano, J., M.1 aLogue, M.1 aNapolioni, V.1 aGreicius, M., D.  uhttps://chs-nhlbi.org/node/9664