Evidence map›Paper›PMID 40335834›Full record

ArticleMetabolomics : Official journal of the Metabolomic Society2025

Associations of APOE variants with sphingomyelin and cholesterol metabolites across the life-course in diverse populations.

Sanghun Lee, Rachel S Kelly, Yulu Chen, Mohammad Waqas, Kevin M Mendez, Julian Hecker, Georg Hahn, Sharon M Lutz, Juan C Celedón, Clary B Clish and 10 more

Abstract read
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In one paragraph

Article in Metabolomics : Official journal of the Metabolomic Society, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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.

Sanghun LeeDepartment of Medical Consilience, Division of Medicine, Graduate School, Dankook University, Yongin-si, South Korea.
Rachel S KellyChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Yulu ChenChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Mohammad WaqasGenetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Kevin M MendezChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Julian HeckerChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Georg HahnDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Sharon M LutzDepartment of Population Medicine, Harvard Medical School, Harvard Pilgrim Healthcare Institute, Boston, MA, USA.
Juan C CeledónDivision of Pediatric Pulmonary, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, USA.
Clary B ClishMetabolomics Platform, Broad Institute, Cambridge, MA, USA.
Augusto A LitonjuaDivision of Pediatric Pulmonary Medicine, Golisano Children's Hospital at Strong, University of Rochester Medical Center, Rochester, NY, USA.
Qingwen ChenChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Michael McGeachieChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Younjung ChoiGenetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Scott T WeissChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Rudolph E TanziGenetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Christoph LangeChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Dmitry ProkopenkoGenetics and Aging Research Unit, McCance Center for Brain Health, Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. dprokopenko@mgh.harvard.edu.
Jessica A Lasky-SuChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. rejas@channing.harvard.edu.
NHLBI Trans-Omics for Precision Medicine (TOPMed)

Funding

Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2016 to 2020
$12.6M
Proteomics and Metabolomics Core: IDEAL shapes vaccine response, susceptibility to respiratory infectious disease and asthmaU19AI168643 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI OFER LEVY · 2022 to 2026
$10.0M
NHLBI NIH HHS P01 HL132825NIAID NIH HHS U19 AI168643the National Heart, Lung, and Blood Institute R01HL169300the National Heart, Lung, and Blood Institute R01MH129337
6 · The paper itself

Abstract

introductionTwo alleles (ε2 and ε4) in the APOE gene are known to be strongly associated with lipid metabolism disorders, such as dyslipidemia, which are important risk factors for the development of cardiovascular diseases. While prior research has largely centered on adult populations, establishing APOE-lipid associations in infants, children, and adolescents-especially those from historically understudied groups-could inform earlier interventions and treatments.

objectivesThis study aimed to evaluate the dependence of the metabolome on the APOE variants using five diverse cohorts that span infancy through adulthood, comprising a total of over 190,000 individuals.

methodsWe extracted the APOE variants (rs7412 and rs429358) from all cohorts-testing both the ε2 allele (rs7412-T and rs429358-T) and the ε4 allele (rs7412-C and rs429358-C)-and evaluated their associations with the global plasma metabolome which was measured by mass spectrometry-based (Metabolon or Broad Institute) or NMR-based (Nightingale) assays depending on the cohort, using a Bonferroni-corrected significance threshold.

resultsAmong 589 metabolites tested in our discovery population, only six including sphingomyelins and cholesterol were significantly associated with the rs7412/ε2 allele. Sphingomyelin (d18:1/22:0) and cholesterol were negatively associated with ε2 allele (β-value = -0.54 [-0.76, -0.32] p-value = 1.39 × 10

conclusionOur findings support the need for early intervention in lipid levels regardless of age, sex, and ethnicity and further investigations of the APOE variants on risk of various diseases in later life.

Indexed as

Apolipoproteins ECholesterolSphingomyelinsAdolescentAdultAllelesChildChild, PreschoolCohort StudiesFemaleHumansInfantMaleMetabolomeMiddle AgedYoung AdultApoE protein, humanApolipoproteins ECholesterolSphingomyelinsAPOE geneCholesterolMinority populationsSphingomyelins

Identifiers

PMID40335834

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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.