Evidence map›Paper›PMID 39231932›Full record

SynthesisTranslational psychiatry2024

Chromosome X-wide association study in case control studies of pathologically confirmed Alzheimer's disease in a European population.

Emily Simmonds, Ganna Leonenko, Umran Yaman, Eftychia Bellou, Amanda Myers, Kevin Morgan, Keeley Brookes, John Hardy, Dervis Salih, Valentina Escott-Price

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Emily SimmondsDementia Research Institute, Cardiff University, Cardiff, UK.ORCID 0000-0001-5691-597X
Ganna LeonenkoDementia Research Institute, Cardiff University, Cardiff, UK.
Umran YamanInstitute of Neurology, University College London, London, UK.
Eftychia BellouDementia Research Institute, Cardiff University, Cardiff, UK.
Amanda MyersDepartment of Cell Biology, University of Miami, Miller School of Medicine, Miami, FL, USA.
Kevin MorganUniversity of Nottingham, Nottingham, UK.
Keeley BrookesBiosciences, School of Science and Technology, Nottingham Trent University, Nottingham, UK.ORCID 0000-0003-2427-2513
John HardyInstitute of Neurology, University College London, London, UK.
Dervis SalihInstitute of Neurology, University College London, London, UK.
Valentina Escott-PriceDementia Research Institute, Cardiff University, Cardiff, UK. escottpricev@cardiff.ac.uk.ORCID 0000-0003-1784-5483

Funding

Vascular Structure and Function in Cognitive AgingP01AG003949 · NIA · YESHIVA UNIVERSITY · PI Charles B Hall · 1985 to 2026
$73.9M
NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
Alzheimer's Disease Genetics ConsortiumU01AG032984 · NIA · UNIVERSITY OF PENNSYLVANIA · PI SCHELLENBERG, GERARD DAVID · 2009 to 2024
$60.4M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI GRABOWSKI, THOMAS J. · 1985 to 2019
$57.2M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI FAGAN, ANNE · 1985 to 2019
$52.1M
SUPPLEMENT TO ALZHEIMERS DISEASE PATIENT REGISTRYU01AG006786 · NIA · MAYO CLINIC ROCHESTER · PI GRAFF-RADFORD, JONATHAN, JACK, CLIFFORD R. · 1986 to 2023
$49.6M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI LEURGANS, SUE E. · 1991 to 2020
$49.1M
EPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI ALBERT, MARILYN S. · 1985 to 2019
$37.6M
THE PGRN/TDP-43 AXIS IN ALZHEIMER?S DISEASE AND NEURODEGENERATIONP50AG016574 · NIA · MAYO CLINIC ROCHESTER · PI PETERSEN, RONALD C · 1999 to 2018
$36.9M
Research Education ComponentP30AG019610 · NIA · SUN HEALTH RESEARCH INSTITUTE · PI REIMAN, ERIC MICHAEL · 2001 to 2020
$32.5M
Medical Research CouncilNIA NIH HHS P01 AG003949NIA NIH HHS P01 AG017216NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG072980NIA NIH HHS P50 AG005128NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005144NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008671NIA NIH HHS P50 AG016570NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG025711NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG018023NIA NIH HHS R01 AG030146NIA NIH HHS R01 AG032990NIA NIH HHS R01 AG036042NIA NIH HHS R01 AG036836NIA NIH HHS R01 AG048015NIA NIH HHS R01 AG069008NIA NIH HHS RC2 AG036547NIA NIH HHS RF1 AG057473NIA NIH HHS U01 AG006786NIA NIH HHS U01 AG016976NIA NIH HHS U01 AG032984NIA NIH HHS U01 AG046139NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG046161NIA NIH HHS U01 AG061356NIMH NIH HHS P50 MH060451NINDS NIH HHS P50 NS039764NINDS NIH HHS R01 NS080820NINDS NIH HHS U24 NS072026RCUK | Medical Research Council (MRC) UKDRI-3003
6 · The paper itself

Abstract

Although there are several genome-wide association studies available which highlight genetic variants associated with Alzheimer's disease (AD), often the X chromosome is excluded from the analysis. We conducted an X-chromosome-wide association study (XWAS) in three independent studies with a pathologically confirmed phenotype (total 1970 cases and 1113 controls). The XWAS was performed in males and females separately, and these results were then meta-analysed. Four suggestively associated genes were identified which may be of potential interest for further study in AD, these are DDX53 (rs12006935, OR = 0.52, p = 6.9e-05), IL1RAPL1 (rs6628450, OR = 0.36, p = 4.2e-05; rs137983810, OR = 0.52, p = 0.0003), TBX22 (rs5913102, OR = 0.74, p = 0.0003) and SH3BGRL (rs186553004, OR = 0.35, p = 0.0005; rs113157993, OR = 0.52, p = 0.0003), which replicate across at least two studies. The SNP rs5913102 in TBX22 achieves chromosome-wide significance in meta-analysed data. DDX53 shows highest expression in astrocytes, IL1RAPL1 is most highly expressed in oligodendrocytes and neurons and SH3BGRL is most highly expressed in microglia. We have also identified SNPs in the NXF5 gene at chromosome-wide significance in females (rs5944989, OR = 0.62, p = 1.1e-05) but not in males (p = 0.83). The discovery of relevant AD associated genes on the X chromosome may identify AD risk differences and similarities based on sex and lead to the development of sex-stratified therapeutics.

Indexed as

Alzheimer DiseaseChromosomes, Human, XGenome-Wide Association StudyPolymorphism, Single NucleotideAgedAged, 80 and overCase-Control StudiesDEAD-box RNA HelicasesFemaleGenetic Predisposition to DiseaseHumansInterleukin-1 Receptor Accessory ProteinMaleWhite PeopleDEAD-box RNA HelicasesIL1RAPL1 protein, humanInterleukin-1 Receptor Accessory Protein

Identifiers

PMID39231932
PMCPMC11375158

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.