ArticlemedRxiv : the preprint server for health sciences2025
Downward bias in the association between APOE and Alzheimer's Disease using prevalent and by-proxy disease sampling in the All of Us Research Program.
Clayton O Mansel, Valentina Ghisays, Jonathan D Mahnken, Russell H Swerdlow, Eric M Reiman, Jason H Karnes, Joshua C Denny, Olivia J Veatch
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registryThe trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
3 · Its place in the literatureWho cites it
0 citing papers in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
8 authors.
Clayton O ManselDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-0135-7576 Valentina GhisaysBanner Alzheimer's Institute, Phoenix, AZ, USA.
Jonathan D MahnkenDepartment of Biostatistics & Data Science, University of Kansas Medical Center, Kansas City, KS, USA.
Russell H SwerdlowAlzheimer's Disease Research Center, University of Kansas Medical Center, Kansas City, KS, USA.
Eric M ReimanBanner Alzheimer's Institute, Phoenix, AZ, USA.
Jason H KarnesEarly Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, USA.
Joshua C DennyCenter for Precision Health Research, National Human Genome Research Institute, National Institute of Health, Bethesda, MD, USA.
Olivia J VeatchDepartment of Cell Biology and Physiology, University of Kansas Medical Center, Kansas City, KS, USA.
Funding
Technology to Empower Changes in Health (TECH) Network Participant Technologies CenterU24OD023176 · OD · SCRIPPS RESEARCH INSTITUTE, THE · PI TOPOL, ERIC JEFFREY · 2016 to 2022
$204.7MPrecision Medicine Initiative Cohort Program BiobankU24OD023121 · OD · MAYO CLINIC ROCHESTER · PI CEKANOVA, MARIA, CICEK, MINE · 2016 to 2024
$185.5MEnhancing All of Us Data Resources for Nutrition Precision Health: the All of Us Data and Research CenterU2COD023196 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GLAZER, DAVID, HARRIS, PAUL A. · 2016 to 2022
$143.7MAdaptive Platform for Personalized EngagementU24OD023163 · OD · VIGNET, INC. · PI JAIN, PRADUMAN · 2017 to 2020
$102.6MUniversity of Arizona-Banner Health All of Us Research Program OT2OD026549 · OD · UNIVERSITY OF ARIZONA · PI MORENO, FRANCISCO A, REIMAN, ERIC MICHAEL · 2018 to 2023
$78.9MCalifornia Precision Medicine Research Program ConsortiumOT2OD026552 · OD · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ANTON-CULVER, HODA A, OHNO-MACHADO, LUCILA · 2018 to 2023
$73.4MAll of Us PennsylvaniaOT2OD026554 · OD · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI REIS, STEVEN E, VISWESWARAN, SHYAM · 2018 to 2023
$72.1MNew York City Consortium for Precision MedicineOT2OD026556 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BIER, LOUISE E, GHARAVI, ALI G · 2018 to 2023
$67.3MSouthEast Enrollment Center (SEEC) OT2OD026551 · OD · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI CARRASQUILLO, OLVEEN, COLON, VIVIAN · 2018 to 2023
$62.8MSouthern All of Us NetworkOT2OD026548 · OD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI FOUAD, MONA N., KORF, BRUCE R · 2018 to 2023
$60.5MIllinois Precision Medicine Consortium OT2OD026557 · OD · NORTHWESTERN UNIVERSITY AT CHICAGO · PI AHSAN, HABIBUL, ARGOS, MARIA · 2018 to 2023
$60.5MThe New England Precision Medicine Consortium of the All of Us Research ProgramOT2OD026553 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI CLARK, CHERYL RENEE, KARLSON, ELIZABETH W · 2018 to 2023
$58.8MIntramural NIH HHS ZIA HG200417NCATS NIH HHS UL1 TR002366NHLBI NIH HHS R01 HL156993NHLBI NIH HHS R01 HL158686NHLBI NIH HHS R21 HL172036NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG072973NIA NIH HHS T32 AG078114NIGMS NIH HHS P20 GM130423NIH HHS OT2 OD023205NIH HHS OT2 OD023206NIH HHS OT2 OD025276NIH HHS OT2 OD025277NIH HHS OT2 OD025315NIH HHS OT2 OD025337NIH HHS OT2 OD026548NIH HHS OT2 OD026549NIH HHS OT2 OD026550NIH HHS OT2 OD026551NIH HHS OT2 OD026552NIH HHS OT2 OD026553NIH HHS OT2 OD026554NIH HHS OT2 OD026555NIH HHS OT2 OD026556NIH HHS OT2 OD026557NIH HHS OT2 OD036485NIH HHS U24 OD023121NIH HHS U24 OD023163NIH HHS U24 OD023176NIH HHS U2C OD023196
6 · The paper itselfAbstract
Background: Recent genome-wide association studies (GWAS) for Alzheimer's Disease and related dementias (ADRD) have increased statistical power via larger analysis datasets from biobanks by 1) including non-age-matched controls and prevalent cases, and/or 2) including individuals who report a family history of ADRD as proxy cases. However, these methods have the potential to increase noise and distort genetic associations which are important for genomic-informed prevention and treatment of ADRD. Here, we sought to understand how the effect sizes of genetic associations in ADRD could be sensitive to these methodological choices, using Methods: Participants in the Results: The mean age of the cohort was 67±10 years, and it was 58% female; 63% clustered predominantly with European genetic reference populations. Among the participants, 3,107 (1.2%) had prevalent ADRD, 301 (0.1%) had incident ADRD, and 19,910 (7.7%) reported a family history of ADRD (proxy ADRD). Both prevalent and proxy ADRD had attenuated associations with Conclusions: Our study highlights how genetic associations with ADRD can be sensitive to how cases are defined in biobanks like
Identifiers
PMID40568661
PMCPMC12191090
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