Integrative analysis of Mendelian randomization and gene expression profiles reveals a null causal relationship between adiponectin and diabetic retinopathy

ABSTRACT

Observational studies have been conducted to investigate the correlation between adiponectin and diabetic retinopathy (DR), but no consistent relationship has been established. In this study, we employed an integrative analysis that combined Mendelian randomization (MR) and bioinformatics analyses to comprehensively explore the association between DR and adiponectin, aiming to provide a unified answer of their relationship. Using the inverse-variance weighted (IVW) method, the odd ratio (OR) of developing DR per 1 mg/dL increment in genetically predicted log-transformed adiponectin concentration was estimated to be 0.949 (P = 0.557). Other robust MR methods produced consistent results, confirming the absence of a causal effect of adiponectin on DR. Additionally, the expression levels of the six adiponectin-related genes showed no significant differences among normal controls, individuals with diabetes but without DR, and those with DR Furthermore, the biological pathways enriched by these genes were not strongly relevant to DR. At both the individual gene and pathway levels, there were no overlaps between the adiponectin-related genes and the differentially expressed genes, indicating a lack of association between adiponectin and DR based on gene expression profiles. In summary, the integrative analysis, which combined MR and bioinformatics data mining, yielded compelling evidence supporting the notion that adiponectin is not a risk factor for DR.

KEYWORDS:

• Mendelian randomization
• gene expression profiles
• adiponectin
• diabetic retinopathy

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Author’s contributions

Conceived and designed the study: ST. Data analysis: AZ, ST and HW. Result interpretation: CW and HW. Wrote the paper: AZ, ST and CW. All authors reviewed and approved the final manuscript.

Availability of data and materials

Data of microarray experiment used were downloaded from the Gene Expression Omnibus (GEO: https://www.ncbi.nlm.nih.gov/geo/) repository.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21623945.2023.2234522

Additional information

Funding

This study was supported by Jilin Province Scientific and Technological Department (YDZJ202201ZYTS121) and the Interdisciplinary Integration and Innovation Project of Jilin University (JLUXKJC2021ZZ05), and The First Hospital of Jilin University (JDYY11202035 and 04027150002). The funding body had no roles in the design of the study and collection, analysis and interpretation of data and in writing the manuscript.