Evidence mapPaperPMID 41821549Full record

ArticleTherapeutic advances in endocrinology and metabolism2026

Contribution of DNA methylation predicted leptin to all-cause, cancer, and cardiovascular mortality among US adults aged 50 years and older: findings from NHANES 1999-2002.

Yuxin Fan, Li Ding, Junhe Wang, Qi Li, Hua Shu, Shaofang Tang, Baoping Wang, Gang Hu, Yun Shen, Ming Liu

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Article in Therapeutic advances in endocrinology and metabolism, 2026. 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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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Yuxin FanDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Li DingDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Junhe WangDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.ORCID https://orcid.org/0009-0002-6055-610X
Qi LiDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Hua ShuDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Shaofang TangDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Baoping WangDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin, China.
Gang HuDivision of Population and Public Health Science, Pennington Biomedical Research Center, Baton Rouge, LA, USA.ORCID https://orcid.org/0000-0002-6172-8017
Yun ShenDivision of Population and Public Health Science, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.ORCID https://orcid.org/0000-0002-9850-122X
Ming LiuDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, Tianjin 300052, China.

Funding

Louisiana Clinical and Translational Science CenterU54GM104940 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2025 to 2025
$3.9M
NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

Background: Epigenetic biomarkers may provide novel insights into long-term health risk. DNA methylation (DNAm) predicted leptin has been proposed as an epigenetic proxy related to metabolic regulation, but its association with mortality remains underexplored. Objectives: To examine the association between DNAm-predicted leptin levels and all-cause, cardiovascular, and cancer mortality among US adults using The National Health and Nutrition Examination Survey (NHANES) data. Design: Population-based cohort analysis with linkage to the National Death Index. Methods: We analyzed 2531 participants from NHANES 1999-2002 with available DNAm-predicted leptin derived from whole-blood methylation profiles. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality outcomes across quartiles of DNAm-predicted leptin, with sequential adjustment for potential confounders. Subgroup and sensitivity analyses were performed to evaluate robustness. Results: Over a mean follow-up of 17.1 years, 1360 deaths occurred. DNAm-predicted leptin showed a J-shaped association with all-cause mortality. In fully adjusted models, HRs for all-cause mortality were 1.28 (95% CI: 1.00-1.62) for Quartile 1, 1.00 (reference) for Quartile 2, 1.32 (95% CI: 1.01-1.73) for Quartile 3, and 1.35 (95% CI: 1.11-1.64) for Quartile 4. After full adjustment, DNAm-predicted leptin was not statistically significantly associated with cancer mortality, while cardiovascular mortality risk was higher in Quartile 4 compared with Quartile 2. Conclusion: DNAm-predicted leptin was associated with all-cause mortality in a J-shaped pattern, with elevated risk at both lower and higher levels. Associations with cancer mortality were not statistically significant after adjustment, and evidence for cardiovascular mortality was limited to the highest quartile. Larger studies are needed to validate these findings and clarify cause-specific associations. Trial registration: Not applicable.

Indexed as

cancercardiovascular diseaseDNA methylationepigeneticsleptinmortalityNHANES

Identifiers

PMID41821549
PMCPMC12976403

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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 Socratic graph.