Journal
JOURNAL OF CLINICAL MEDICINE
Volume 11, Issue 20, Pages -Publisher
MDPI
DOI: 10.3390/jcm11206014
Keywords
systemic sclerosis; mendelian randomization; obesity
Categories
Funding
- MCIN/AEI [RTI2018101332-B-100, IJC2018-038026-I, IJC2019-040080-I, PRE2019-087586]
- ERDF A way of making Europe - European Union
- Red de Investigacion en Inflamacion y Enfermedades Reumaticas (RIER) from Instituto de Salud Carlos III [RD16/0012/0013]
- ESF Investing in your future
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Obesity is a known risk factor for immune-mediated diseases, but its role in systemic sclerosis (SSc) is still unclear. This study used genetic correlation analyses and Mendelian randomization methods to investigate the relationship between body fat distribution parameters and SSc. The results showed no genetic correlation or causal relationship between these parameters and SSc, except for a negative causal association between WHRadjBMI and SSc.
Obesity contributes to a chronic proinflammatory state, which is a known risk factor to develop immune-mediated diseases. However, its role in systemic sclerosis (SSc) remains to be elucidated. Therefore, we conducted a two-sample mendelian randomization (2SMR) study to analyze the effect of three body fat distribution parameters in SSc. As instrumental variables, we used the allele effects described for single nucleotide polymorphisms (SNPs) in different genome-wide association studies (GWAS) for SSc, body mass index (BMI), waist-to-hip ratio (WHR) and WHR adjusted for BMI (WHRadjBMI). We performed local (pHESS) and genome-wide (LDSC) genetic correlation analyses between each of the traits and SSc and we applied several Mendelian randomization (MR) methods (i.e., random effects inverse-variance weight, MR-Egger regression, MR pleiotropy residual sum and outlier method and a multivariable model). Our results show no genetic correlation or causal relationship between any of these traits and SSc. Nevertheless, we observed a negative causal association between WHRadjBMI and SSc, which might be due to the effect of gastrointestinal complications suffered by the majority of SSc patients. In conclusion, reverse causality might be an especially difficult confounding factor to define the effect of obesity in the onset of SSc.
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