Methodological challenges, solution pathways, and future priorities in Mendelian randomization research: a bibliometric and content analysis
5 affiliations
- 1Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau, China
- 2School of Medicine, Jiaying University, Meizhou, Guangdong, China
- 3College of Public Health, Zhengzhou University, Zhengzhou, Henan, China
- 4Emergency Department, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, China
- 5Department of Nephrology, People’s Hospital of Longhua, Shenzhen, Guangdong, China
Abstract
Objective To characterize the global landscape, intellectual structure, major methodological challenges, dominant solution pathways, and future priorities in Mendelian randomization (MR) research.MethodsArticles and reviews on MR within the predefined 2003–2025 eligibility window were retrieved from the Web of Science Core Collection (WOSCC) and Scopus to construct a primary corpus (A-corpus). After field harmonization and hierarchical deduplication, conventional bibliometric analyses were performed. A problem-driven B-corpus was constructed by applying a prespecified terminology dictionary to titles, abstracts, and keywords, followed by manual eligibility review of dictionary-positive records and independent double coding across four dimensions: methodological challenges, solution pathways, future priorities, and solution orientations.ResultsThe A-corpus comprised 21,346 publications retrieved under the predefined 2003–2025 eligibility window; a small number of eligible records carried 2026 early-access or indexing metadata in the source databases. Strict dictionary screening identified 10,598 candidate records; 10,291 were excluded after eligibility review and 307 publications were retained in the final B-corpus. In the B-corpus, horizontal pleiotropy was the most frequent methodological challenge (90/307, 29.3%), mixed sensitivity framework was the dominant solution pathway (107/307, 34.9%), and reproducible reporting pipeline (45/307, 14.7%), mechanism-aware inference (36/307, 11.7%), and omics integration (34/307, 11.1%) were the leading explicitly coded future-priority categories. Inter-coder reliability ranged from moderate to almost perfect across dimensions, with Cohen’s kappa values of 0.434 for methodological challenges, 0.531 for solution pathways, 0.703 for future priorities, and 0.897 for solution orientations.ConclusionThis combined bibliometric and content analysis identified major publication patterns, recurrent methodological challenges, commonly reported solution pathways, and explicitly stated future priorities in MR research. The findings show the continuing prominence of causal-validity concerns alongside attention to mechanistic interpretation, reproducibility, generalizability, and translation; they describe patterns in the published literature rather than establishing the comparative scientific validity or clinical value of individual MR methods.
Related
- Associations of Blood Lipid Traits with Cognitive-Related Outcomes and Their Sensitivity to APOE-Region Instrumental Variables: A Mendelian Randomization and Colocalization Study
- The relationship between genetic bone mineral density and spinal stenosis: a Mendelian randomization and cohort study
- Hypoglycemic Agent Targets and Susceptibility to Lower Respiratory Infection: A Pharmacogenomic Mendelian Randomization Study
- A robust and accurate two-sample Mendelian randomization method with a large number of genetic variants
- Monocyte Immunometabolic Axis Linking Type 2 Diabetes to Coronary Artery Disease Revealed by Multi-Omics Integration and Mendelian Randomization
BibTeX
@article{zhang2026methodological,
title = {{Methodological challenges, solution pathways, and future priorities in Mendelian randomization research: a bibliometric and content analysis}},
author = {Jiapeng Zhang and Jiapeng Zhang and Ying Xiao and Feifei Feng and Meiyi Feng and Dan Jiang and Ling Wang},
journal = {Frontiers in Genetics},
year = {2026},
month = oct,
doi = {10.3389/fgene.2026.1853737},
url = {https://doi.org/10.3389/fgene.2026.1853737},
note = {CC BY},
}
RIS
TY - JOUR
TI - Methodological challenges, solution pathways, and future priorities in Mendelian randomization research: a bibliometric and content analysis
AU - Jiapeng Zhang
AU - Jiapeng Zhang
AU - Ying Xiao
AU - Feifei Feng
AU - Meiyi Feng
AU - Dan Jiang
AU - Ling Wang
PY - 2026
DA - 2026/10/26
JO - Frontiers in Genetics
DO - 10.3389/fgene.2026.1853737
UR - https://doi.org/10.3389/fgene.2026.1853737
AB - Objective To characterize the global landscape, intellectual structure, major methodological challenges, dominant solution pathways, and future priorities in Mendelian randomization (MR) research.MethodsArticles and reviews on MR within the predefined 2003–2025 eligibility window were retrieved from the Web of Science Core Collection (WOSCC) and Scopus to construct a primary corpus (A-corpus). After field harmonization and hierarchical deduplication, conventional bibliometric analyses were performed. A problem-driven B-corpus was constructed by applying a prespecified terminology dictionary to titles, abstracts, and keywords, followed by manual eligibility review of dictionary-positive records and independent double coding across four dimensions: methodological challenges, solution pathways, future priorities, and solution orientations.ResultsThe A-corpus comprised 21,346 publications retrieved under the predefined 2003–2025 eligibility window; a small number of eligible records carried 2026 early-access or indexing metadata in the source databases. Strict dictionary screening identified 10,598 candidate records; 10,291 were excluded after eligibility review and 307 publications were retained in the final B-corpus. In the B-corpus, horizontal pleiotropy was the most frequent methodological challenge (90/307, 29.3%), mixed sensitivity framework was the dominant solution pathway (107/307, 34.9%), and reproducible reporting pipeline (45/307, 14.7%), mechanism-aware inference (36/307, 11.7%), and omics integration (34/307, 11.1%) were the leading explicitly coded future-priority categories. Inter-coder reliability ranged from moderate to almost perfect across dimensions, with Cohen’s kappa values of 0.434 for methodological challenges, 0.531 for solution pathways, 0.703 for future priorities, and 0.897 for solution orientations.ConclusionThis combined bibliometric and content analysis identified major publication patterns, recurrent methodological challenges, commonly reported solution pathways, and explicitly stated future priorities in MR research. The findings show the continuing prominence of causal-validity concerns alongside attention to mechanistic interpretation, reproducibility, generalizability, and translation; they describe patterns in the published literature rather than establishing the comparative scientific validity or clinical value of individual MR methods.
SN - 1664-8021
ER -