Evidence map›Paper›PMID 35023831›Full record

ArticleeLife2022

GWAS and ExWAS of blood mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia.

Michael Chong, Pedrum Mohammadi-Shemirani, Nicolas Perrot, Walter Nelson, Robert Morton, Sukrit Narula, Ricky Lali, Irfan Khan, Mohammad Khan, Conor Judge and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 5 pooled it
–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

71 citing papers in PubMed, 5 syntheses or guidelines pooled it.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Michael ChongDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.ORCID 0000-0002-0555-4622
Pedrum Mohammadi-ShemiraniDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.ORCID 0000-0001-6740-7858
Nicolas PerrotPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Walter NelsonCentre for Data Science and Digital Health, Hamilton Health Sciences, Hamilton, Canada.
Robert MortonDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.ORCID 0000-0003-0099-4167
Sukrit NarulaPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Ricky LaliPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Irfan KhanDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Mohammad KhanPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Conor JudgePopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Tafadzwa MachipisaDepartment of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada.
Nathan CawtePopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Martin O'DonnellPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Marie PigeyrePopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Loubna AkhabirPopulation Health Research Institute, David Braley Cardiac, Vascular and Stroke Research Institute, Hamilton Health Sciences, Hamilton, Canada.
Guillaume ParéDepartment of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada.ORCID 0000-0002-6795-4760

Funding

CIHRWellcome Trust 099313/B/12/AWellcome Trust 203930/B/16/Z
6 · The paper itself

Abstract

Background: Mitochondrial DNA copy number (mtDNA-CN) is an accessible blood-based measurement believed to capture underlying mitochondrial (MT) function. The specific biological processes underpinning its regulation, and whether those processes are causative for disease, is an area of active investigation. Methods: We developed a novel method for array-based mtDNA-CN estimation suitable for biobank-scale studies, called 'automatic mitochondrial copy (AutoMitoC).' We applied AutoMitoC to 395,781 UKBiobank study participants and performed genome- and exome-wide association studies, identifying novel common and rare genetic determinants. Finally, we performed two-sample Mendelian randomization to assess whether genetically low mtDNA-CN influenced select MT phenotypes. Results: Overall, genetic analyses identified 71 loci for mtDNA-CN, which implicated several genes involved in rare mtDNA depletion disorders, deoxynucleoside triphosphate (dNTP) metabolism, and the MT central dogma. Rare variant analysis identified Conclusions: Altogether, our genetic findings indicate that mtDNA-CN is a complex biomarker reflecting specific MT processes related to mtDNA regulation, and that these processes are causally related to human diseases. Funding: No funds supported this specific investigation. Awards and positions supporting authors include: Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarships Doctoral Award (MC, PM); CIHR Post-Doctoral Fellowship Award (RM); Wellcome Trust Grant number: 099313/B/12/A; Crasnow Travel Scholarship; Bongani Mayosi UCT-PHRI Scholarship 2019/2020 (TM); Wellcome Trust Health Research Board Irish Clinical Academic Training (ICAT) Programme Grant Number: 203930/B/16/Z (CJ); European Research Council COSIP Grant Number: 640580 (MO); E.J. Moran Campbell Internal Career Research Award (MP); CISCO Professorship in Integrated Health Systems and Canada Research Chair in Genetic and Molecular Epidemiology (GP).

Indexed as

AdultAgedBiomarkersDementiaDNA Copy Number VariationsDNA, MitochondrialExome SequencingFemaleGene DosageGenome-Wide Association StudyHumansMaleMendelian Randomization AnalysisMiddle AgedMitochondriaPhenotypeBiomarkersDNA, Mitochondrialdementiageneticsgenome-wide association studygenomicshumanmedicineMendelian randomizationmitochondrial DNA copy number

Identifiers

PMID35023831
PMCPMC8865845

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.