Language
English
Publication Date
10-10-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-64927-5
PMID
41073432
PMCID
PMC12514310
PubMedCentral® Posted Date
10-10-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Type 2 diabetes is associated with a range of non-cardiovascular non-oncologic comorbidities. To move beyond associations and evaluate causal effects between type 2 diabetes genetic predisposition and 21 comorbidities, we apply Mendelian randomization analysis using genome-wide association studies across multiple genetic ancestries. Additionally, leveraging eight mechanistic clusters of type 2 diabetes genetic profiles, each representing distinct biological pathways, we investigate causal links between cluster-stratified type 2 diabetes genetic predisposition and comorbidity risk. We identify causal effects of type 2 diabetes genetic predisposition driven by distinct genetic clusters. For example, the risk-increasing effects of type 2 diabetes genetic predisposition on cataracts and erectile dysfunction are primarily attributed to adiposity and glucose regulation mechanisms, respectively. We observe opposing effect directions across different genetic ancestries for depression, asthma and chronic obstructive pulmonary disease. Our findings leverage the heterogeneity underpinning type 2 diabetes genetic predisposition to prioritize biological mechanisms underlying causal relationships with comorbidities.
Keywords
Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Comorbidity, Mendelian Randomization Analysis, Pulmonary Disease, Chronic Obstructive, Male, Polymorphism, Single Nucleotide, Asthma, Depression, Female, Cataract, Risk Factors
Published Open-Access
yes
Recommended Citation
Arruda, Ana Luiza; Bocher, Ozvan; Taylor, Henry J; et al., "The Effect of Type 2 Diabetes Genetic Predisposition on Non-Cardiovascular Comorbidities" (2025). Faculty, Staff and Students Publications. 7729.
https://digitalcommons.library.tmc.edu/baylor_docs/7729