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This study performed sex-stratified genome-wide association study (GWAS) using single nucleotide polymorphism (SNP) from the Alzheimer's Disease Genetics Consortium (ADGC) sample with European ancestry. Subjects with individual-pairwise genetic relationship matrix (GRM) > 0.1 were excluded from analyses to ensure sample independence.
GWAS of 38,043,163 SNPs were separately performed in males and females using logistic regressions implemented in PLINK 1.9. Age at disease onset of AD (or age at the first visit for the control group), cohort indicators, and the top 10 principal components were included as covariates. A total of 8,682 males (4,010 cases and 4,672 controls) and 12,772 females (5,705 cases and 7,067 controls) were included combining cohorts of both ADGC phase 1 and 2. (Wang, et al., 2021).
Result of the high genetic correlation indicates overall similar genetic architecture of AD in both sexes at the genome-wide averaged level. Our study suggests that clinically observed sex differences may arise from sex-specific variants with small effects or more complicated mechanisms involving epigenetic alterations, sex chromosomes, or gene-environment interactions.
The p-value data is available to all users using the link below; however, gaining access to the complete dataset requires a formal data request.
This study was supported by National Institutes of Health, R56AG061163, R01MH118281; The Alzheimer's Disease Genetics Consortium (ADGC) were supported by a grant from the National Institute on Aging/National Institutes of Health UO1AG032984 and complete acknowledgments for ADGC are detailed in the ADGC website http://www.adgenetics.org/content/acknowledgements.