Evidence map›Paper›PMID 38712163›Full record

ArticlemedRxiv : the preprint server for health sciences2024

The Role of X Chromosome in Alzheimer's Disease Genetics.

Michael E Belloy, Yann Le Guen, Ilaria Stewart, Joachim Herz, Richard Sherva, Rui Zhang, Victoria Merritt, Matthew S Panizzon, Richard L Hauger, VA Million Veteran Program and 4 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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 registry

The 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 literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Michael E BelloyDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-7748-9033
Yann Le GuenDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6649-8364
Ilaria StewartDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Joachim HerzCenter for Translational Neurodegeneration Research, Department of Molecular Genetics University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.ORCID 0000-0002-8506-3400
Richard ShervaBiomedical Genetics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID 0000-0003-2133-1493
Rui ZhangNational Center for PTSD, Behavioral Sciences Division, VA Boston Healthcare System, Boston, MA, USA.
Victoria MerrittCenter of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.ORCID 0000-0001-5683-4168
Matthew S PanizzonDepartment of Psychiatry, University of California San Diego, La Jolla, CA, USA.ORCID 0000-0002-6449-2097
Richard L HaugerCenter of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.ORCID 0000-0003-1509-1868
VA Million Veteran Program
J Michael GazianoMillion Veteran Program (MVP) Coordinating Center, VA Boston Healthcare System, Boston, MA, USA.ORCID 0000-0002-5384-9767
Mark LogueBiomedical Genetics, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID 0000-0001-9347-7892
Valerio NapolioniSchool of Biosciences and Veterinary Medicine, University of Camerino, Camerino, Italy.ORCID 0000-0002-4378-6838
Michael D GreiciusDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-5462-9037

Funding

Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6M
Large Scale Genome SequencingU54HG003079 · NHGRI · WASHINGTON UNIVERSITY · PI DUTCHER, SUSAN K · 2004 to 2016
$445.7M
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
Project 1U19AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE/RES/EDU · PI MONICA G. RIVERA-MINDT · 2016 to 2026
$226.7M
Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8M
TRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
VCID and Stroke in a Bi-racial National CohortU01NS041588 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI CUSHMAN, MARY, HOWARD, GEORGE · 2002 to 2022
$96.0M
Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Richard B. LIPTON · 1985 to 2026
$73.9M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Smartphone-Based "Burst" Cognitive AssessmentsP01AG003991 · NIA · WASHINGTON UNIVERSITY · PI JOHN MORRIS · 1985 to 2026
$69.5M
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HHS R01 AG048927NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG050595NIA NIH HHS R01 AG054076NIA NIH HHS R01 AG057777NIA NIH HHS R01 AG057907NIA NIH HHS R01 AG058501NIA NIH HHS R01 AG060747NIA NIH HHS R01 AG064877NIA NIH HHS R37 AG015473NIA NIH HHS R56 AG051876NIA NIH HHS R56 AG064877NIA NIH HHS RC2 AG036528NIA NIH HHS RC2 AG036547NIA NIH HHS RC2 AG036650NIA NIH HHS RC4 AG039085NIA NIH HHS RF1 AG015473NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG053303NIA NIH HHS RF1 AG054014NIA NIH HHS RF1 AG054023NIA NIH HHS RF1 AG054052NIA NIH HHS RF1 AG054074NIA NIH HHS RF1 AG057440NIA NIH HHS RF1 AG057519NIA NIH HHS RF1 AG058066NIA NIH HHS RF1 AG058267NIA NIH HHS RF1 AG058501NIA NIH HHS U01 AG006781NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG010483NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046170NIA NIH HHS U01 AG049505NIA NIH HHS U01 AG049506NIA NIH HHS U01 AG049507NIA NIH HHS U01 AG049508NIA NIH HHS U01 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6 · The paper itself

Abstract

Importance: The 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. Objectives: 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. Design: 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. Setting: 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. Participants: 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. Main Outcome and Measures: Risk for AD (odds ratio; OR) with 95% confidence intervals (CI). Associations were considered at X-chromosome-wide (P-value<1e-5) and genome-wide (P-value<5e-8) significance. Results: Analyses included 1,152,284 non-Hispanic White European ancestry subjects (57.3% females), including 138,558 cases. 6 independent genetic loci passed X-chromosome-wide significance, with 4 showing support for causal links between the genetic signal for AD and expression of nearby genes in brain and non-brain tissues. One of these 4 loci passed conservative genome-wide significance, with its lead variant centered on an intron of Conclusion and Relevance: We performed the first large-scale XWAS of AD and identified the novel

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