Evidence map›Paper›PMID 42811415›Full record

ArticleDiabetes, obesity & metabolism2026

Genetically Proxied GIP-GIPR Pathway Perturbation and Fracture Risk.

Wenjie Cheng, Weijie Liu, Jie Wei, Chao Zeng, Houchen Lyu, Sizheng Steven Zhao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, obesity & metabolism, 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

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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

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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

6 authors.

Wenjie ChengCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.ORCID https://orcid.org/0009-0000-0999-0934
Weijie LiuCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
Jie WeiDepartment of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.ORCID https://orcid.org/0000-0003-3510-8241
Chao ZengDepartment of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Houchen LyuDepartment of Orthopaedics, The Chinese PLA General Hospital, Beijing, Beijing, China.ORCID https://orcid.org/0000-0002-0128-0062
Sizheng Steven ZhaoCentre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Funding

Arthritis UK 21173Arthritis UK 21754Arthritis UK 21755Arthritis UK Career Development Fellowship 23258Manchester Biomedical Research Centre NIHR203308
6 · The paper itself

Abstract

aimsTo determine whether genetic proxies for incretin pathway perturbation are associated with fracture risk and bone mineral density, providing human genetic evidence relevant to the skeletal safety of incretin-based therapies. MATERIALS AND

methodsWe conducted drug-target Mendelian randomisation using cis genetic variants near GIP, GIPR, GCG, GLP1R in 401 983 unrelated UK Biobank participants. Instruments were scaled to 1 kg/m

resultsGIP-GIPR perturbation was associated with lower odds of fractures at major osteoporotic sites when scaled to lower BMI (OR 0.80, 95% CI 0.66-0.98) or lower HbA1c. Associations were similar for combined spine-and-hip fractures under both scaling approaches (OR 0.68, 0.49-0.94). Genome-wide liability to lower BMI or HbA1c did not show the same fracture associations as GIP-GIPR perturbation. GCG-GLP1R estimates were imprecise. Genetically proxied incretin pathway perturbation was not associated with eBMD. In Cox analyses, GIP-GIPR genetic risk score was associated with lower risk of fractures at major osteoporotic sites (HR 0.976, 0.959-0.992) and combined spine-and-hip fractures (HR 0.971, 0.946-0.996).

conclusionsHuman genetic evidence suggests an association between genetically proxied GIP-GIPR pathway perturbation and lower fracture risk, supporting fracture-focused evaluation of GIPR-targeting therapies in clinical and post-marketing studies.

Indexed as

Fractures, BoneGastric Inhibitory PolypeptideOsteoporotic FracturesReceptors, Gastrointestinal HormoneAgedBody Mass IndexBone DensityDiabetes Mellitus, Type 2FemaleGenetic Risk ScoreGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinHumansIncretinsMaleMendelian Randomization AnalysisGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorGlycated HemoglobinIncretinsReceptors, Gastrointestinal Hormonecohort studyincretin therapyrisk predictionType 2 diabetes

Identifiers

PMID42811415
PMCPMC13731033

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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.