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 genomewide
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.MCIN/AEI RTI2018101332-B-100
IJC2018-038026-I
IJC2019-040080-I
PRE2019-087586"ERDF A way of making Europe" - European UnionRed de Investigacion en Inflamacion y Enfermedades Reumaticas (RIER) from Instituto de Salud Carlos III RD16/0012/0013ESF Investing in your futur