| Title: | The Genetic Associations Between Kidney Stones, Obesity, Type 2 Diabetes, and Hypertension |
| Journal: | Mayo Clinic Proceedings |
| Published: | 20 Sep 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40974350/ |
| DOI: | https://doi.org/10.1016/j.mayocp.2025.04.030 |
| URL: | https://pmc.ncbi.nlm.nih.gov/articles/PMC12453589/ |
Publication 19446
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
OBJECTIVE: Investigate shared genetic changes that contribute to the association of kidney stones with cardiometabolic comorbidities.</p>
PATIENTS AND METHODS: Genome-wide association studies (GWAS) and meta-analyses were performed using the UK Biobank, Mayo Clinic Biobank, and FinnGen, complemented by secondary genetic association analyses.</p>
RESULTS: Genetic correlation analyses confirmed modest but significant positive associations between kidney stones and hypertension, obesity, and type 2 diabetes (rg=0.14 ∼ 0.19, all P<.001). Single nucleotide variants near FTO (for expansion of gene symbols, use search tool at www.genenames.org) were identified as shared risk loci across all conditions. Mendelian randomization analyses demonstrated that higher body mass index (BMI) and waist-hip ratio (WHR) significantly increased the risk of kidney stones, type 2 diabetes, and hypertension. Subsequent GWAS analyses adjusting for BMI or WHR revealed a slightly reduced yet significant genetic correlation between kidney stones and type 2 diabetes (BMI-adjusted: rg=0.18; 95% CI, 0.07 to 0.28; P=.001; WHR-adjusted: rg=0.16; 95% CI, 0.06 to 0.25; P<.001), whereas the association of kidney stones with hypertension was nearly eliminated. A multi-trait analysis of GWAS identified one potential shared risk locus between BMI-adjusted kidney stones and type 2 diabetes on chromosome 6 near LINC02537. Further analyses indicated this locus is associated with thyroid-stimulating hormone and free thyroxine levels.</p>
CONCLUSION: Our study highlights a critical role for shared obesity-related genetic changes in the comorbid relationship between kidney stones and cardiometabolic conditions. There are additional genetic features related to thyroid function that are shared between kidney stones and type 2 diabetes, which appear to be independent of obesity.</p>
14 Keywords
- Body Mass Index
- Diabetes Mellitus, Type 2
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Hypertension
- Kidney Calculi
- Male
- Mendelian Randomization Analysis
- Middle Aged
- Obesity
- Polymorphism, Single Nucleotide
- Waist-Hip Ratio
10 Authors
- Le-Ting Zhou
- Isaac W Stark
- Ahmed E Ali
- Muthuvel Jayachandran
- Zejfa Haskic
- Peter C Harris
- Kevin Koo
- Shannon K McDonnell
- Nicholas B Larson
- John C Lieske
1 Application
| Application ID | Title |
|---|---|
| 130923 | Identification of shared genetic disorders of kidney stones and chronic kidney disease |
Enabling scientific discoveries that improve human health