An association study exploring the genetic relationship of psoriatic arthritis and obesity

Welsh, Cassidy (2022) An association study exploring the genetic relationship of psoriatic arthritis and obesity. Masters thesis, Memorial University of Newfoundland.

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Abstract

Objective: To determine if there is a genetic component causing psoriatic arthritis (PsA) patients to have higher BMIs when compared to the general population. Method: 696 obese samples were identified from a previous genetic study on obesity which were genotyped using a PsA SNP panel. 650 PsA patients who were examined for PsA related anthropometric measures were genotyped using an obesity SNP panel. An obesity panel was created using a gene prioritization method to create a 46 SNP obesity-weighted panel. Two separate quantitative trait analyses were performed to obtain the association between BMI and genotype of the subsequent panels using a linear regression model. Bonferroni correction was used to adjust for multiple comparisons. Results: Genotypes of two PsA-weighted SNPs, rs10782001 (FBXL19) and rs3131382 (HLA-B*39), showed a significant difference with BMI. Patients with the FBXL19 variant had an average BMI in the presence of GG genotype of 37.2 kg/m² vs 34.3 kg/m² for the AA genotype (p=0.0007). Patients with the HLA-B*39:05 variant had an average BMI with the TT genotype of 47.1 kg/m2 vs 35.4 kg/m² for the CC genotype (p=0.00005). One obesity-weighted SNP, rs11915371 (SAMMSON/FOXP1), showed a significant difference of BMI between genotypes in PsA patients. The average BMI of those with the CC genotype was 32.42 kg/m² compared to an average BMI of 29.77 kg/m² with the TT genotype (p=0.0009). Conclusion: Homozygotes for the minor allele of SNPs within HLA-B*39, FBXL19, and SAMMSON/FOXP1 have shown to have an increased BMI, suggesting a potential genetic link between these genes and PsA and obesity.

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