This dataset contains the sex stratified and interaction summary statistics memory and memory slopes published in Eissman, et al, 2024 (Alzheimer’s and Dementia, PMID pending). Memory scores were obtained from multiple ADSP cohorts (ACT, ADNI, NACC, ROS/MAP/MARS) at baseline and longitudinally. Memory scores were harmonized between cohorts using item-level data. Memory slopes were calculated with a null linear mixed-effects regression where the slope and the intercept were allowed to vary for each participant. Genotype data in each study underwent standard quality control and imputation onto the TOPMed reference panel (genome build 38).

All GWAS described were performed in males, in females, and with a sex-interaction. Covariates included baseline age and the first 5 genetic ancestry principal components, and additionally the sex-interaction GWAS contained a SNP-by-sex interaction term. We performed GWAS in ACT, ADNI, NACC, and ROS/MAP/MARS separately. Within each cohort, GWAS were performed among NHW and among NHB participants separately. X-Wide Association Studies (XWAS) were performed identically to the GWAS, except that male genotypes were coded as 0/2 (instead of 0/1) to account for X-chromosome dosage differences between males and females. Within each ancestry group, we additionally performed sex-stratified and sex-interaction GWAS and XWAS subgroup analyses, by first limiting the sample to cognitively unimpaired and then limiting to cognitively impaired. Male, female, and sex-interaction individual cohort GWAS were meta-analyzed implementing a fixed-effects model with beta and standard error input. Meta-analyses were performed within each ancestry group and furthermore within each diagnostic category mentioned above. Meta-analysis results were restricted to SNPs present in 3-4 (out of 4) cohorts. Results were further filtered to retain SNPs with a stratum specific MAF of >1%. These filtered meta-analysis results were leveraged for the cross-ancestry meta-analyses which was performed in the same manner as the previous ones. SNPs were retained if they were present in both ancestry groups. The summary statistics included here include both autosomal and X chromosome variants from the cross-ancestry meta-analysis.

Dr. Logan Dumitrescu
Vanderbilt University Medical Center

The study was funded by NIH Grants (F31 AG077791, R01 AG059716, U24 AG041689).

Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer's Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

For investigators using Sex-specific genetic architecture of late-life memory performance data:

Data collection was supported through funding by NIA grants P30AG10161 (ROS), P30AG72975, R01AG15819 (ROSMAP; genomics and RNAseq), R01AG17917 (MAP), R01AG22018, R01AG30146, R01AG36042 (5hC methylation, ATACseq), RC2AG036547 (H3K9Ac), R01AG36836 (RNAseq), R01AG48015 (monocyte RNAseq) RF1AG57473 (single nucleus RNAseq), U01AG32984 (genomic and whole exome sequencing), U01AG46152 (ROSMAP AMP-AD, targeted proteomics), U01AG46161(TMT proteomics), U01AG61356 (whole genome sequencing, targeted proteomics, ROSMAP AMP-AD), the Illinois Department of Public Health (ROSMAP), and the Translational Genomics Research Institute (genomic). The results published here are in whole or in part based on data obtained from the AD Knowledge Portal (https://adknowledgeportal.synapse.org). Study data were provided by the Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago. Additional phenotypic data can be requested at www.radc.rush.edu.

Data collection and sharing for ADNI were supported by National Institutes of Health Grant U01-AG024904 and Department of Defense (award number W81XWH-12-2-0012). ADNI is also funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.

The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Ann McKee, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD).

The Alzheimer’s Disease Genetics Consortium supported genotyping, and data processing of samples through National Institute on Aging (NIA) grants U01-AG032984. Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689). The Adult Changes in Thought Study, based at Kaiser Permanente Health Research Institute of Washington and the University of Washington, is supported through U19-AG066567.

Additional support includes R01-AG073439, U24-AG074855, K01-AG049164, R01-AG059716, R01-AG061518, R21-AG05994, K12-HD043483, K24-AG046373, HHSN311201600276P, S10-OD023680, R01-AG034962, R01-NS100980, R01-AG056534, P30-AG010161, R01-AG15819, R01-AG17917, U01-AG46152, R01-AG048927, U19-AG068753, U01 AG058654, R01-AG062634, R01-AG048927, U19-AG068753, K23:AG045966, the Nancy and Buster Alvord Endowment (C. D. K.), the Vanderbilt Clinical Translational Science Award (UL1-TR000445), the Vanderbilt Memory and Alzheimer’s Center, and the Vanderbilt Alzheimer’s Disease Research Center (P20-AGAG068082). Part of Figure 1 created with BioRender.com. Additional funding also includes F31-AG077791.

The ADSP Phenotype Harmonization Consortium (ADSP-PHC) is funded by NIA (U24 AG074855, U01 AG068057 and R01 AG059716). The ADSP-PHC cohorts include: Adult Changes in Thought (ACT, U01 AG006781, U19 AG066567), the Alzheimer’s Disease Centers (ADC, P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD), the Alzheimer's Disease Neuroimaging Initiative (ADNI), funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California, the Memory ang Aging Project at the Knight-ADRC (Knight-ADRC), supported by NIH grants R01AG064614, R01AG044546, RF1AG053303, RF1AG058501, U01AG058922 and R01AG064877 to Carlos Cruchaga. The recruitment and clinical characterization of research participants at Washington University was supported by NIH grants P30AG066444, P01AG03991, and P01AG026276. Data collection and sharing for this project was supported by NIH grants RF1AG054080, P30AG066462, R01AG064614 and U01AG052410.

This work was supported by access to equipment made possible by the Hope Center for Neurological Disorders, the Neurogenomics and Informatics Center (NGI: https://neurogenomics.wustl.edu/) and the Departments of Neurology and Psychiatry at Washington University School of Medicine; the Minority Aging Research Study (MARS, R01 AG22018, R01 AG42210), the National Alzheimer’s Coordinating Center (NACC, U01 AG016976, U24 AG072122),the National Institute on Aging Late Onset Alzheimer's Disease Family Study (NIA- LOAD, U24 AG056270), the Religious Orders Study (ROS, P30 AG10161, P30 AG72975, R01 AG15819, R01 AG42210), the RUSH Memory and Aging Project (MAP, R01 AG017917, R01 AG42210), the National Institute on Aging Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS, U24AG041689) at the University of Pennsylvania, and the Genome Center for Alzheimer’s Disease (U54AG05247), funded by NIA.

The Alzheimer's Disease Genetics Consortium supported collection and genotyping of samples used in this study through National Institute on Aging (NIA) grants U01AG032984 and RC2AG036528. Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689-01), The Center for Applied Genomics at the Children’s Hospital of Philadelphia Research Institute performed genotyping of samples. The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADRCs: P30 AG062429 (PI James Brewer, MD, PhD), P30 AG066468 (PI Oscar Lopez, MD), P30 AG062421 (PI Bradley Hyman, MD, PhD), P30 AG066509 (PI Thomas Grabowski, MD), P30 AG066514 (PI Mary Sano, PhD), P30 AG066530 (PI Helena Chui, MD), P30 AG066507 (PI Marilyn Albert, PhD), P30 AG066444 (PI John Morris, MD), P30 AG066518 (PI Jeffrey Kaye, MD), P30 AG066512 (PI Thomas Wisniewski, MD), P30 AG066462 (PI Scott Small, MD), P30 AG072979 (PI David Wolk, MD), P30 AG072972 (PI Charles DeCarli, MD), P30 AG072976 (PI Andrew Saykin, PsyD), P30 AG072975 (PI David Bennett, MD), P30 AG072978 (PI Neil Kowall, MD), P30 AG072977 (PI Robert Vassar, PhD), P30 AG066519 (PI Frank LaFerla, PhD), P30 AG062677 (PI Ronald Petersen, MD, PhD), P30 AG079280 (PI Eric Reiman, MD), P30 AG062422 (PI Gil Rabinovici, MD), P30 AG066511 (PI Allan Levey, MD, PhD), P30 AG072946 (PI Linda Van Eldik, PhD), P30 AG062715 (PI Sanjay Asthana, MD, FRCP), P30 AG072973 (PI Russell Swerdlow, MD), P30 AG066506 (PI Todd Golde, MD, PhD), P30 AG066508 (PI Stephen Strittmatter, MD, PhD), P30 AG066515 (PI Victor Henderson, MD, MS), P30 AG072947 (PI Suzanne Craft, PhD), P30 AG072931 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Justin Miller, PhD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD) Samples from the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which receives government support under a cooperative agreement grant (U24 AG21886) awarded by the National Institute on Aging (NIA), were used in this study. We thank contributors who collected samples used in this study, as well as patients and their families, whose help and participation made this work possible. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Rush University grants P30 AG010161, R01 AG019085, R01 AG15819, R01 AG17917, R01 AG030146, R01 AG01101, RC2 AG036650, R01 AG22018, UO1 AG06781, UO1 HG004610.