Evidence map›Paper›PMID 34880091›Full record

ArticleNeurology2022

Mitochondrial DNA Copy Number as a Marker and Mediator of Stroke Prognosis: Observational and Mendelian Randomization Analyses.

Michael Robert Chong, Sukrit Narula, Robert Morton, Conor Judge, Loubna Akhabir, Nathan Cawte, Nazia Pathan, Ricky Lali, Pedrum Mohammadi-Shemirani, Ashkan Shoamanesh and 4 more

Open access · hybridAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 17% of its field
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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

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  16. Nuclear genetic control of mtDNA copy number and heteroplasmy in humans.medRxiv : the preprint server for health sciences · 2023
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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

14 authors at 1 institution in 3 countries.

Michael Robert ChongFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Sukrit NarulaFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Robert MortonFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.ORCID 0000-0003-0099-4167
Conor JudgeFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Loubna AkhabirFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Nathan CawteFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Nazia PathanFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Ricky LaliFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Pedrum Mohammadi-ShemiraniFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Ashkan ShoamaneshFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Martin O'DonnellFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Salim YusufFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Peter LanghorneFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK.
Guillaume ParéFrom the Population Health Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., A.S., M.O., S.Y., G.P.), David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences; Thrombosis and Atherosclerosis Research Institute (M.R.C., S.N., R.M., C.J., L.A., N.C., N.P., R.L., P.M.-S., S.Y., G.P.); Department of Biochemistry and Biomedical Sciences (M.R.C., G.P.), Departments of Pathology and Molecular Medicine (M.R.C., R.M., P.M.-S., G.P.) and Medicine (L.A., A.S., S.Y., G.P.), Michael G. DeGroote School of Medicine, and Department of Health Research Methods, Evidence, and Impact (S.N., R.L., S.Y., G.P.), McMaster University, Hamilton, Ontario, Canada; National University of Ireland Galway (C.J., M.O.); and Institute of Cardiovascular and Medical Sciences (P.L.), University of Glasgow, UK. pareg@mcmaster.ca.
Ollscoil na Gaillimhe – University of Galway · IE

Funding

CIHR 399497
6 · The paper itself

Abstract

BACKGROUND AND

objectivesLow buffy coat mitochondrial DNA copy number (mtDNA-CN) is associated with incident risk of stroke and poststroke mortality; however, its prognostic utility has not been extensively explored. Our goal was to investigate whether low buffy coat mtDNA-CN is a marker and causal determinant of poststroke outcomes using epidemiologic and genetic studies.

methodsFirst, we performed association testing between baseline buffy coat mtDNA-CN measurements and 1-month poststroke outcomes in 3,498 cases of acute, first stroke from 25 countries from the international, multicenter case-control study Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World (INTERSTROKE). Then, we performed 2-sample mendelian randomization analyses to evaluate potential causative effects of low mtDNA-CN on 3-month modified Rankin Scale (mRS) score. Genetic variants associated with mtDNA-CN levels were derived from the UK Biobank study (N = 383,476), and corresponding effects on 3-month mRS score were ascertained from the Genetics of Ischemic Stroke Functional Outcome (GISCOME; N = 6,021) study.

resultsA 1-SD lower mtDNA-CN at baseline was associated with stroke severity (baseline mRS score: odds ratio [OR] 1.27, 95% confidence interval [CI] 1.19-1.36; DISCUSSION: Buffy coat mtDNA-CN is a novel and robust marker of poststroke prognosis that may also be a causal determinant of poststroke outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that low buffy coat mtDNA-CN (>1 SD) was associated with worse baseline severity and 1-month outcomes in patients with ischemic or hemorrhagic stroke.

Indexed as

DNA, MitochondrialStrokeCase-Control StudiesDNA Copy Number VariationsHumansMendelian Randomization AnalysisPrognosisRisk FactorsDNA, Mitochondrial

Identifiers

PMID34880091
PMCPMC8826461
OpenAlexW4200194650

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