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. 2022 Oct 12;11(20):6014.
doi: 10.3390/jcm11206014.

The Effect of Body Fat Distribution on Systemic Sclerosis

Gonzalo Villanueva-Martin  1 , Marialbert Acosta-Herrera  2 , Martin Kerick  1 , Elena López-Isac  1 , Carmen P Simeón  3 , José L Callejas  4 , Shervin Assassi  5 , Lorenzo Beretta  6 , International SSc Group, Australian Scleroderma Interest Group Asig, Yannick Allanore  7 , Susanna M Proudman  8 , Mandana Nikpour  8 , Carmen Fonseca  9 , Christopher P Denton  9 , Timothy R D J Radstake  10 , Maureen D Mayes  5 , Xia Jiang  11   12   13 , Javier Martin  1 , Lara Bossini-Castillo  14   15
Affiliations

The Effect of Body Fat Distribution on Systemic Sclerosis

Gonzalo Villanueva-Martin et al. J Clin Med. .

Abstract

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.

Keywords: mendelian randomization; obesity; systemic sclerosis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure A1
Figure A1
Local genetic correlation, local genetic variance and local SNP heritability between SSc and (a) BMI, (b) WHR and (c) WHRadjBMI.
Figure A2
Figure A2
MR leave-one-out sensitivity analyses for: (A) BMI, (B) WHR and (C) WHRadjBMI.
Figure 1
Figure 1
Schematic representation of the study design. The study is divided into several phases, i.e., selection of the instrumental variables for the outcome and the exposures, data harmonization and generation of different Mendelian randomization models.
Figure 2
Figure 2
Pairwise global genetic correlation observed between the three obesity-related exposures and SSc. * = p > 0.05 (suggestive for statistical significance); ** = p > 0.00625 (Bonferroni-corrected).
See this image and copyright information in PMC

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