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

Front Immunol. 2024 Mar 14:15:1328297. doi: 10.3389/fimmu.2024.1328297. eCollection 2024.

Abstract

Background: 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.

Methods: 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 (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.

Results: We 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.

Conclusions: 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.

Keywords: Mendelian randomization; genome-wide cross-trait analysis; lipidemic; obesity; psoriasis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoproteins / genetics
  • Genome-Wide Association Study*
  • Humans
  • Obesity / genetics
  • Phenotype
  • Psoriasis* / genetics

Substances

  • Apolipoproteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was financially supported by the National Natural Science Foundation of China (82004363, U23A6012, U20A20397), Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-C-202204), Science and Technology Planning Project of Guangdong Province (2023B1212060063, 2020B1111100006, 2020B1212030006), State Key Laboratory of Dampness Syndrome of Chinese Medicine Special Fund (SZ2021ZZ29, SZ2021ZZ45), Basic and Applied Basic Research of Guangzhou City-University Joint Funding Project (202201020317, 202201020332), Youth Talent Promotion Project of China Association of Traditional Chinese Medicine (2021-QNRC2-B07), Research Fund for Zhaoyang Talents of Guangdong Provincial Hospital of Chinese Medicine (ZY2022KY10), and Guangdong Provincial Hospital of Chinese Medicine Special Fund (YN2023ZH16, YN2021DB03).