The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis

Kisielnicka, Anna; Sobalska‐Kwapis, Marta; Purzycka-Bohdan, Dorota; Nedoszytko, Bogusław; Zabłotna, Monika; Seweryn, Michał; Strapagiel, Dominik; Nowicki, Roman; Reich, Adam; Samotij, Dominik; Szczęch, Justyna; Krasowska, Dorota; Bartosińska, Joanna; Lesiak, Aleksandra; Barasińska, Paulina; Owczarczyk‐Saczonek, Agnieszka; Czerwińśka, Joanna; Szepietowski, Jacek C.; Batycka-Baran, Aleksandra; Czajkowski, Rafał; Górecka-Sokołowska, Magdalena; Rudnicka, Lidia; Czuwara, Joanna; Szczerkowska‐Dobosz, Aneta

doi:10.3390/ijms23137396

Cited by 13 publications

(13 citation statements)

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“…Psoriasis is a complex disease involving various pathogenic and immunological mechanisms ( 17 , 96 ). Although >100 psoriasis susceptibility loci have been identified through GWAS in different countries and ethnicities ( 96 – 101 ), there have been limited studies on genetic susceptibility loci in Taiwan ( 102 , 103 ). The present study conducted GWAS and PRS to identify 92 novel genomic markers and identified 61 previously reported genomic markers associated with psoriasis.…”

Section: Discussionmentioning

confidence: 99%

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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Psoriasis is a chronic inflammatory dermatological disease, and there is a lack of understanding of the genetic factors involved in psoriasis in Taiwan. To establish associations between genetic variations and psoriasis, a genome-wide association study was performed in a cohort of 2,248 individuals with psoriasis and 67,440 individuals without psoriasis. Using the ingenuity pathway analysis software, biological networks were constructed. Human leukocyte antigen (HLA) diplotypes and haplotypes were analyzed using Attribute Bagging (HIBAG)-R software and chi-square analysis. The present study aimed to assess the potential risks associated with psoriasis using a polygenic risk score (PRS) analysis. The genetic association between single nucleotide polymorphisms (SNPs) in psoriasis and various human diseases was assessed by phenome-wide association study. METAL software was used to analyze datasets from China Medical University Hospital (CMUH) and BioBank Japan (BBJ). The results of the present study revealed 8,585 SNPs with a significance threshold of P<5×10 −8 , located within 153 genes strongly associated with the psoriasis phenotype, particularly on chromosomes 5 and 6. This specific genomic region has been identified by analyzing the biological networks associated with numerous pathways, including immune responses and inflammatory signaling. HLA genotype analysis indicated a strong association between HLA-A*02:07 and HLA-C*06:02 in a Taiwanese population. Based on our PRS analysis, the risk of psoriasis associated with the SNPs identified in the present study was quantified. These SNPs are associated with various dermatological, circulatory, endocrine, metabolic, musculoskeletal, hematopoietic and infectious diseases. The meta-analysis results indicated successful replication of a study conducted on psoriasis in the BBJ. Several genetic loci are significantly associated with susceptibility to psoriasis in Taiwanese individuals. The present study contributes to our understanding of the genetic determinants that play a role in susceptibility to psoriasis. Furthermore, it provides valuable insights into the underlying etiology of psoriasis in the Taiwanese community.

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Section: Discussionmentioning

confidence: 99%

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Yang,

Liu,

et al. 2024

Mol Med Rep

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“…Furthermore, the association between obesity and psoriasis has received affirmation from animal studies ( 42 ). A study that compared the genetic background of obesity in psoriasis patients with that of healthy controls through GWAS revealed a connection between 11 genetic polymorphisms and abnormal body weight in psoriasis patients ( 43 ). Findings from previous studies have also suggested that weight loss can lead to improved clinical outcomes, including a reduction in psoriatic flares ( 15 , 44 – 46 ).…”

Section: Discussionmentioning

confidence: 99%

A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis

Wu,

Huang,

Chen

et al. 2024

Front. Immunol.

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BackgroundObesity and dyslipidemia, major global health concerns, have been linked to psoriasis, but previous studies faced methodological limitations and their shared genetic basis remains unclear. This study examines various obesity-related and lipidemic traits as potential contributors to psoriasis development, aiming to clarify their genetic associations and potential causal links.MethodsSummary statistics from genome-wide association studies (GWAS) conducted for obesity-related traits (body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-hip ratio adjusted for the body mass index (WHRadjBMI)) and lipidemic traits (high-density lipoprotein (HDL), LDL, triglyceride (TG), total Cholesterol (TC), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), and apolipoprotein E (apoE)) and psoriasis, all in populations of European ancestry, were used. We quantified genetic correlations, identified shared loci and explored causal relationship across traits.ResultsWe found positive genetic correlation between BMI and psoriasis (rg=0.22, p=2.44×10-18), and between WHR and psoriasis (rg=0.19, p=1.41×10-12). We further found the positive genetic correlation between psoriasis and WHRadjBMI(rg=0.07, p=1.81×10-2) the genetic correlation, in while the effect of BMI was controlled for. We identified 14 shared loci underlying psoriasis and obesity-related traits and 43 shared loci between psoriasis and lipidemic traits via cross-trait meta-analysis. Mendelian randomization (MR) supported the causal roles of BMI (IVW OR=1.483, 95%CI=1.333-1.649), WHR (IVW OR=1.393, 95%CI=1.207-1.608) and WHRadjBMI (IVW OR=1.18, 95%CI=1.047-1.329) in psoriasis, but not observe any significant association between lipidemic traits and the risk of psoriasis. Genetic predisposition to psoriasis did not appear to affect the risk of obesity and lipidemic traits.ConclusionsAn intrinsic link between obesity-related traits and psoriasis has been demonstrated. The genetic correlation and causal role of obesity-related traits in psoriasis highlight the significance of weight management in both the prevention and treatment of this condition.

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“…Afterward, DNA samples underwent a PCR reaction for sex verification. The same method was performed as in our previous study [ 73 ].…”

Section: Methodsmentioning

confidence: 99%

Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis

Purzycka-Bohdan

Nedoszytko

Sobalska‐Kwapis

et al. 2023

IJMS

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Recent studies have indicated a key role of the impaired suppressive capacity of regulatory T cells (Tregs) in psoriasis (PsO) pathogenesis. However, the genetic background of Treg dysfunctions remains unknown. The aim of this study was to evaluate the association of PsO development with selected single nucleotide polymorphisms (SNPs) of genes in which protein products play a significant role in the regulation of differentiation and function of Tregs. There were three study groups in our research and each consisted of different unrelated patients and controls: 192 PsO patients and 5605 healthy volunteers in the microarray genotyping group, 150 PsO patients and 173 controls in the ARMS–PCR method group, and 6 PsO patients and 6 healthy volunteers in the expression analysis group. The DNA microarrays analysis (283 SNPs of 57 genes) and ARMS–PCR method (8 SNPs in 7 genes) were used to determine the frequency of occurrence of SNPs in selected genes. The mRNA expression of selected genes was determined in skin samples. There were statistically significant differences in the allele frequencies of four SNPs in three genes (TNF, IL12RB2, and IL12B) between early-onset PsO patients and controls. The lowest p-value was observed for rs3093662 (TNF), and the G allele carriers had a 2.73 times higher risk of developing early-onset PsO. Moreover, the study revealed significant differences in the frequency of SNPs and their influence on PsO development between early- and late-onset PsO. Based on the ARMS–PCR method, the association between some polymorphisms of four genes (IL4, IL10, TGFB1, and STAT3) and the risk of developing PsO was noticed. Psoriatic lesions were characterized with a lower mRNA expression of FOXP3, CTLA4, and IL2, and a higher expression of TNF and IL1A in comparison with unaffected skin. In conclusion, the genetic background associated with properly functioning Tregs seems to play a significant role in PsO pathogenesis and could have diagnostic value.

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The Analysis of a Genome-Wide Association Study (GWAS) of Overweight and Obesity in Psoriasis

Cited by 13 publications

References 50 publications

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

Genome‑wide association study and polygenic risk scores predict psoriasis and its shared phenotypes in Taiwan

A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis

Assessment of the Potential Role of Selected Single Nucleotide Polymorphisms (SNPs) of Genes Related to the Functioning of Regulatory T Cells in the Pathogenesis of Psoriasis

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