Evidence map›Paper›PMID 42394584›Full record

ArticleJournal of diabetes research2026

Multiomics Mendelian Randomization Identifies Lactylation-Related Molecular Traits in Type 1 Diabetes.

Yu Ding, Shiyang Gao, Lingwen Ying, Jie Tang, Guoying Chang, Yiguo Huang, Tingting Yu, Xin Li, Xiumin Wang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of diabetes research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

Yu DingDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0002-0833-924X
Shiyang GaoDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0009-0005-1338-6891
Lingwen YingDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0001-6240-9221
Jie TangDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0003-3747-3031
Guoying ChangDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0003-0701-3544
Yiguo HuangDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0002-4049-6667
Tingting YuDepartment of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0001-6030-9614
Xin LiCAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China, cas.cn.ORCID https://orcid.org/0000-0002-2122-7461
Xiumin WangDepartment of Endocrinology and Metabolism, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China, shsmu.edu.cn.ORCID https://orcid.org/0000-0002-9012-1273

Funding

2024-National Clinical Key Specialty Construction Project 10000015Z155080000004National Natural Science Foundation of China 82170910Science and Technology Development Fund of Pudong New Area PKJ2025-Y03Special Research Project of National Health Commission Capacity Building and Continuing Education Center GWJJZX20251003002Youth Clinical Cadre Hospital Fund of Shanghai Children's Medical Center QN-SCMC2023-5
6 · The paper itself

Abstract

backgroundLactylation is a posttranslational modification involved in cellular metabolic and immune processes. Although dysregulated lactate metabolism has been implicated in type 1 diabetes (T1D), the genetic relevance of lactylation-related molecular traits remains poorly defined.

methodsSummary-data-based Mendelian randomization (SMR) was applied to integrate blood-derived methylation/expression/protein quantitative trait loci (mQTLs/eQTLs/pQTLs) for 353 lactylation-related genes with a T1D genome-wide association study (7467 cases and 10,218 controls). The HEIDI test evaluated heterogeneity. Shared genetic signals were assessed by Bayesian colocalization. Associations identified in the discovery analysis were replicated in the FinnGen_R12_T1D and FinnGen_R9_E4_DM1NEU cohorts. mQTL-eQTL SMR analysis evaluated methylation-expression regulatory relationships. Steiger directionality testing and GTEx tissue eQTL analyses were performed for prioritized genes.

resultsSMR prioritized PDAP1, PNKD, and HMGB1 as candidate genes associated with T1D. At the DNA methylation level, methylation at cg05715492 (PDAP1) was positively associated with T1D risk (OR = 1.29, 95% CI: 1.09-1.53), whereas cg05991184 (PNKD) showed an inverse association (OR = 0.73, 95% CI: 0.59-0.90). cg22712983, cg26786924, and cg04880052 in PNKD exhibited positive associations. cg25251738 (HMGB1) methylation was inversely associated with risk (OR = 0.85, 95% CI: 0.75-0.97). At the expression level, genetically predicted PDAP1 (OR = 0.26, 95% CI: 0.10-0.66) and HMGB1 (OR = 0.45, 95% CI: 0.22-0.91) expressions were inversely associated with T1D risk, whereas PNKD expression was positively associated (OR = 1.13, 95% CI: 1.04-1.23). mQTL-eQTL SMR analyses demonstrated significant methylation-expression associations at PDAP1, PNKD, and HMGB1 loci. Steiger directionality testing supported the observed associations. In GTEx datasets, higher PNKD expression was associated with increased T1D risk in both whole blood and spleen.

conclusionPNKD, PDAP1, and HMGB1 were prioritized as lactylation-related candidate genes associated with T1D risk through integrated genetic analyses. This finding generates hypothesis for future investigations into the potential involvement of lactylation-related pathways in T1D pathogenesis.

Indexed as

Diabetes Mellitus, Type 1Protein Processing, Post-TranslationalDNA MethylationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisMultiomicsQuantitative Trait Locigenome-wide association studylactylationMendelian randomizationmultiomicsposttranslational protein modificationquantitative trait locitype 1 diabetes

Identifiers

PMID42394584
PMCPMC13329454

What Socratic holds

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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.