Evidence mapPaperPMID 42174728Full record

ArticleGenome medicine2026

GWAS-by-subtraction reveals new genetic architecture and health implications of type 2 diabetes-independent gestational diabetes mellitus.

Siquan Zhou, Zhichang Ran, Yanliu Li, Jiayuan He, Xin Yuan, Yuanqi Hu, Xiaoyu Wang, Ruirui Li, Yujie Xu, Ciling Yan and 2 more

Abstract read
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

12 authors.

Siquan ZhouWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Zhichang RanWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Yanliu LiWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Jiayuan HeWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Xin YuanWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Yuanqi HuWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China.
Xiaoyu WangLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Maternal & Child Nutrition Center, West China Second University Hospital, Ministry of Education, Sichuan University, 17 Renminnan Road 3rd Section, Chengdu, 61041, China.
Ruirui LiLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Maternal & Child Nutrition Center, West China Second University Hospital, Ministry of Education, Sichuan University, 17 Renminnan Road 3rd Section, Chengdu, 61041, China.
Yujie XuLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Maternal & Child Nutrition Center, West China Second University Hospital, Ministry of Education, Sichuan University, 17 Renminnan Road 3rd Section, Chengdu, 61041, China.
Ciling YanTownship Health Center of Shanquan Town Longquanyi District, Chengdu, 610100, China.
Jingyuan XiongWest China School of Public Health and West China Fourth Hospital, Sichuan University, 16 Renminnan Road 3rd Section, Chengdu, 610041, China. jzx0004@tigermail.auburn.edu.ORCID http://orcid.org/0000-0001-9354-862X
Guo ChengLaboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Maternal & Child Nutrition Center, West China Second University Hospital, Ministry of Education, Sichuan University, 17 Renminnan Road 3rd Section, Chengdu, 61041, China. gcheng@scu.edu.cn.ORCID http://orcid.org/0000-0002-0945-5728

Funding

National Natural Science Foundation of China U25A20154Science and Technology Department of Sichuan Province 2025ZNSFSC0641
6 · The paper itself

Abstract

backgroundThe etiology of gestational diabetes mellitus (GDM) is constituted by both type 2 diabetes (T2D)-dependent and T2D-independent mechanisms. However, existing studies have evaluated the impact of T2D-dependent loci only for GDM, which limits the power to assess to what extent genetic variants or biological pathways are specific to GDM.

methodsWe subtracted the genetic effects of a genome-wide association study (GWAS) data for T2D from a GWAS data for GDM to reveal loci linked with T2D-independent components of GDM using genomic structural equation model (SEM). In the discovery stage of GWAS-by-subtraction, we used GWAS summary statistics of GDM and T2D from the FinnGen study as input latent variables (16,802 GDM cases and 237,816 controls; 71,728 T2D cases and 369,007 controls). In the replication stage, we adopted the summary statistics from a previously reported GWAS for GDM and T2D as input (21,263 GDM cases and 301,918 controls; 50,409 T2D cases and 523,897 controls). We functionally annotated variants with genome-wide significance, and performed comprehensive analyses including transcriptome-wide and proteome-wide associations, summary-data-based mendelian randomization, linkage disequilibrium score regression, and Mendelian randomization, to explore genetic patterns for T2D-dependent and -independent components of GDM.

resultsWe found 69 independent genome-wide significant loci associated with the T2D-independent components of GDM for discovery stage, of which 49 SNPs are not significant in the GWAS for GDM used as input. T2D-independent components of GDM showed only genetic correlation with birth weight dependent on maternal genetic effect (rg = 0.19; P = 0.01), whilst T2D-dependent components of GDM showed genetic correlation with birth weight dependent on fetal genetic effect (rg = -0.22; P = 4.76 × 10

conclusionsWe identified independent genetic components, loci and genes of GDM that may have been previously masked by T2D, providing more accurate targets for early detection and management of GDM.

Indexed as

Diabetes, GestationalDiabetes Mellitus, Type 2Genetic Predisposition to DiseaseGenome-Wide Association StudyFemaleHumansPolymorphism, Single NucleotidePregnancyGenome-wide association studyGenomic structural equation modelGestational diabetes mellitusGWAS-by-subtractionType 2 diabetes

Identifiers

PMID42174728
PMCPMC13371021

What Socratic 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 Socratic graph.