The Effect of Body Fat Distribution on Systemic Sclerosis
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Villanueva Martin, Gonzalo; Acosta Herrera, Marialbert; Kerick, Martin; López Isac, Elena; Callejas Rubio, José Luis; International SSc Group; Australian Scleroderma Interest Group (ASIG); Martín Ibáñez, Javier; Bossini Castillo, Lara MaríaEditorial
MDPI
Materia
Systemic sclerosis Mendelian randomization Obesity
Date
2022-10-12Referencia bibliográfica
Villanueva-Martin, G... [et al.]. The Effect of Body Fat Distribution on Systemic Sclerosis. J. Clin. Med. 2022, 11, 6014. [https://doi.org/10.3390/jcm11206014]
Sponsorship
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 futureAbstract
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.