Evidence map›Paper›PMID 40355419›Full record

ArticleNature communications2025

Twin pair analysis uncovers links between DNA methylation, mitochondrial DNA quantity and obesity.

Aino Heikkinen, Vivienne F C Esser, Seung Hyuk T Lee, Sara Lundgren, Antti Hakkarainen, Jesper Lundbom, Juho Kuula, Per-Henrik Groop, Sini Heinonen, Sergio Villicaña and 10 more

Abstract readTwin Study
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

20 authors.

Aino HeikkinenInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. aino.heikkinen@helsinki.fi.ORCID http://orcid.org/0000-0001-5770-6475
Vivienne F C EsserCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-1851-7927
Seung Hyuk T LeeDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-0943-6076
Sara LundgrenInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Antti HakkarainenHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.ORCID http://orcid.org/0000-0002-7367-2532
Jesper LundbomHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Juho KuulaHUS Medical Imaging Center, Radiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Per-Henrik GroopFolkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.ORCID http://orcid.org/0000-0003-4055-6954
Sini HeinonenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Sergio VillicañaDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-2455-7095
Jordana T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.ORCID http://orcid.org/0000-0002-3858-5986
Alice MaguoloEpigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0002-8921-2012
Emma NilssonEpigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.
Charlotte LingEpigenetics and Diabetes Unit, Department of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.ORCID http://orcid.org/0000-0003-0587-7154
Allan VaagDepartment of Clinical Sciences in Malmö, Lund University Diabetes Centre, Scania University Hospital, Malmö, Sweden.
Päivi PajukantaDepartment of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-6423-8056
Jaakko KaprioInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-3716-2455
Kirsi H PietiläinenObesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-8522-1288
Shuai LiCentre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-8696-8594
Miina OllikainenInstitute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland. miina.ollikainen@helsinki.fi.ORCID http://orcid.org/0000-0003-3661-7400

Funding

Academy of Finland (Suomen Akatemia) #314383, #266286Academy of Finland (Suomen Akatemia) (#328685, #307339, #297908 and #251316Academy of Finland (Suomen Akatemia) #338417Department of Health | National Health and Medical Research Council (NHMRC) GNT2017373Novo Nordisk Fonden (Novo Nordisk Foundation) #NNF20OC0060547, #NNF17OC0027232, #NNF10OC1013354Novo Nordisk Fonden (Novo Nordisk Foundation) #NNF23SA0083953Wellcome Trust
6 · The paper itself

Abstract

Alterations in mitochondrial metabolism in obesity may indicate disrupted communication between mitochondria and nucleus, and DNA methylation may influence this interplay. Here, we leverage data from the Finnish Twin Cohort study subcohort (n = 173; 86 full twin pairs, 1 singleton), including comprehensive measurements of obesity-related outcomes, mitochondrial DNA quantity and nuclear DNA methylation levels in adipose and muscle tissue, to identify one CpG at SH3BP4 significantly associated with mitochondrial DNA quantity in adipose tissue (FDR < 0.05). We also show that SH3BP4 methylation correlates with its gene expression. Additionally, we find that 14 out of the 35 obesity-related traits display significant associations with both SH3BP4 methylation and mitochondrial DNA quantity in adipose tissue. We use data from TwinsUK and the Scandinavian T2D-discordant monozygotic twin cohort, to validate the observed associations. Further analysis using ICE FALCON suggests that mitochondrial DNA quantity, insulin sensitivity and certain body fat measures are causal to SH3BP4 methylation. Examining mitochondrial DNA quantity and obesity-related traits suggests causation from mitochondrial DNA quantity to obesity, but unmeasured within-individual confounding cannot be ruled out. Our findings underscore the impact of mitochondrial DNA quantity on DNA methylation and expression of the SH3BP4 gene within adipose tissue, with potential implications for obesity.

Indexed as

Adaptor Proteins, Signal TransducingDNA MethylationDNA, MitochondrialObesityAdipose TissueAdultAgedCohort StudiesCpG IslandsFemaleFinlandHumansInsulin ResistanceMaleMiddle AgedMitochondriaAdaptor Proteins, Signal TransducingDNA, Mitochondrial

Identifiers

PMID40355419
PMCPMC12069627

What Socratic holds

Textmetadata
LicenceCC BY
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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 Socratic graph.