AUTHOR=Wu Yuan , Huang Mengfen , Chen Xueru , Wu Jingjing , Li Li , Wei Jianan , Lu Chuanjian , Han Ling , Lu Yue 

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

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1328297

DOI=10.3389/fimmu.2024.1328297

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Obesity 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.</p></sec><sec><title>Methods</title><p>Summary 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 (WHR<sub>adj</sub>BMI)) 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.</p></sec><sec><title>Results</title><p>We found positive genetic correlation between BMI and psoriasis (r<sub>g</sub>=0.22, p=2.44×10<sup>-18</sup>), and between WHR and psoriasis (r<sub>g</sub>=0.19, p=1.41×10<sup>-12</sup>). We further found the positive genetic correlation between psoriasis and WHR<sub>adj</sub>BMI(r<sub>g</sub>=0.07, p=1.81×10<sup>-2</sup>) 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 WHR<sub>adj</sub>BMI (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.</p></sec><sec><title>Conclusions</title><p>An 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.</p></sec>