Evidence map›Paper›PMID 41040731›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Evaluating the causal effect of mitochondrial dysfunction on Alzheimer's and Parkinson's disease using Polygenic Risk Scores and Mendelian Randomization.

Aadrita Chatterjee, Brian Alvarez, Rakshya U Sharma, Caroline Jonson, Heather M Wilkins, Judy Pa, Russell H Swerdlow, Alison Goate, Kristine Yaffe, Shea J Andrews

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article 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.

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

10 authors.

Aadrita ChatterjeeDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA Department of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.
Brian AlvarezDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Rakshya U SharmaDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA Department of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.
Caroline JonsonCenter for Alzheimer's and Related Dementias, National Institutes of Health, Bethesda, MD, USA.
Heather M WilkinsDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Judy PaAlzheimer's Disease Cooperative Study (ADCS), Department of Neurosciences, University of California, San Diego, CA, USA.
Russell H SwerdlowDepartment of Neurology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Alison GoateDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0002-0576-2472
Kristine YaffeDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA Department of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.
Shea J AndrewsDepartment of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA Department of Psychiatry and Behavioral Sciences, University of California San Francisco, 505 Parnassus Ave, San Francisco, CA, USA.ORCID 0000-0002-1921-9470

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
University of Kansas Alzheimer's Disease Research Center (KU ADRC)P30AG072973 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Mohammad Haeri · 2021 to 2026
$25.3M
Population Based Research for Alzheimer's Innovation (POP BRAIN)R35AG071916 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI YAFFE, KRISTINE · 2021 to 2024
$3.8M
Relationships between APP and MitochondriaR01AG078186 · NIA · UNIVERSITY OF KANSAS MEDICAL CENTER · PI Heather M. Wilkins · 2023 to 2026
$2.9M
NIA NIH HHS P30 AG072973NIA NIH HHS R01 AG078186NIA NIH HHS R35 AG071916NIA NIH HHS U01 AG024904
6 · The paper itself

Abstract

introductionMitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with AD and PD. We integrate genetic correlation, Polygenic Risk Scores (PRS), and Mendelian Randomization (MR) to assess whether mtDNAcn influences the risk of AD and PD, and evaluate how study-specific factors in mtDNAcn genome-wide association studies (GWAS) may distort these causal estimates.

methodsUsing GWAS of four mtDNAcn measures, AD, AD/dementia, and PD, we evaluated genetic correlations, generated ancestry-normalized PRS in the AD Genetics Consortium (N=27,383), and applied MR methods including Latent Heritable Confounder MR (LHC-MR).

resultsAcross the four mtDNAcn GWAS, only one was consistently associated with AD/dementia and PD, with genetic correlations and PRS analysis showing negative correlations and MR indicating that higher mtDNAcn reduced AD/dementia and PD risk. DISCUSSION: Higher blood-based mtDNAcn was causally associated with reduced risk of AD/dementia and PD, with limited evidence to suggest a bidirectional effect.

Indexed as

Alzheimer’s diseasegenetic correlationsMendelian RandomizationMitochondrial DNA copy numberParkinson’s diseasePolygenic Risk Scores

Identifiers

PMID41040731
PMCPMC12486050

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

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.