Table_5_The relationship between blood lipid and risk of psoriasis: univariable and multivariable Mendelian randomization analysis.docx

BackgroundPsoriasis is a chronic inflammatory skin disease. Dyslipidemia may be a risk factor of psoriasis. But the causal relationship between psoriasis and blood lipid still remains uncertain.
MethodsThe two data of blood lipid were obtained from UK Biobank (UKBB) and Global Lipid Genetics Consortium Results (GLGC). The primary and secondary database were from large publicly available genome-wide association study (GWAS) with more than 400,000 and 170,000 subjects of European ancestry, respectively. The psoriasis from Finnish biobanks of FinnGen research project for psoriasis, consisting of 6,995 cases and 299,128 controls. The single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) were used to assess the total and direct effects of blood lipid on psoriasis risk.
ResultsSVMR estimates in primary data of blood lipid showed low-density lipoprotein cholesterol (LDL-C) (odds ratio (OR): 1.11, 95%, confidence interval (CI): 0.99−1.25, p = 0.082 in stage 1; OR: 1.15, 95% CI: 1.05−1.26, p = 0.002 in stage 2; OR: 1.15, 95% CI: 1.04−1.26, p = 0.006 in stage 3) and triglycerides (TG) (OR: 1.22, 95% CI: 1.10−1.35, p = 1.17E-04 in stage 1; OR: 1.15, 95% CI: 1.06−1.24, p = 0.001 in stage 2; OR: 1.14, 95% CI: 1.05−1.24, p = 0.002 in stage 3) had a highly robust causal relationship on the risk of psoriasis. However, there were no robust causal associations between HDL-C and psoriasis. The SVMR results in secondary data of blood lipid were consistent with the primary data. Reverse MR analysis showed a causal association between psoriasis and LDL-C (beta: -0.009, 95% CI: -0.016− -0.002, p = 0.009) and HDL-C (beta: -0.011, 95% CI: -0.021− -0.002, p = 0.016). The reverse causation analyses results between psoriasis and TG did not reach significance. In MVMR of primary data of blood lipid, the LDL-C (OR: 1.05, 95% CI: 0.99–1.25, p = 0.396 in stage 1; OR: 1.07, 95% CI: 1.01–1.14, p = 0.017 in stage 2; OR: 1.08, 95% CI: 1.02–1.15, p = 0.012 in stage 3) and TG (OR: 1.11, 95% CI: 1.01–1.22, p = 0.036 in stage 1; OR: 1.09, 95% CI: 1.03–1.15, p = 0.002 in stage 2; OR: 1.07, 95% CI: 1.01–1.13 p = 0.015 in stage 3) positively correlated with psoriasis, and there had no correlation between HDL-C and psoriasis. The results of the secondary analysis were consistent with the results of primary analysis.
ConclusionsMendelian randomization (MR) findings provide genetic evidence for causal link between psoriasis and blood lipid. It may be meaningful to monitor and control blood lipid level for a management of psoriasis patients in clinic.

【背景】银屑病是一种慢性炎症性皮肤病。血脂异常可能是银屑病的危险因素，但二者之间的因果关联至今仍未明确。
【方法】本研究的两项血脂数据分别来源于英国生物样本库（UK Biobank, UKBB）与全球脂质遗传学联盟（Global Lipid Genetics Consortium, GLGC）。主数据库与次数据库均来自公开的大型全基因组关联研究（Genome-Wide Association Study, GWAS），纳入的欧洲裔受试者人数分别超过40万与17万。银屑病数据集来自FinnGen研究项目的芬兰生物样本库银屑病队列，共纳入6995例病例与299128例对照。本研究采用单变量孟德尔随机化（Single-Variable Mendelian Randomization, SVMR）与多变量孟德尔随机化（Multivariable Mendelian Randomization, MVMR）两种方法，评估血脂对银屑病发病风险的总效应与直接效应。
【结果】基于血脂主数据库的单变量孟德尔随机化分析结果显示，低密度脂蛋白胆固醇（Low-Density Lipoprotein Cholesterol, LDL-C）（阶段1：比值比（Odds Ratio, OR）=1.11，95%置信区间（Confidence Interval, CI）=0.99~1.25，p=0.082；阶段2：OR=1.15，95%CI=1.05~1.26，p=0.002；阶段3：OR=1.15，95%CI=1.04~1.26，p=0.006）与甘油三酯（Triglycerides, TG）（阶段1：OR=1.22，95%CI=1.10~1.35，p=1.17×10^-4；阶段2：OR=1.15，95%CI=1.06~1.24，p=0.001；阶段3：OR=1.14，95%CI=1.05~1.24，p=0.002）与银屑病发病风险存在显著且稳健的因果关联。而高密度脂蛋白胆固醇（High-Density Lipoprotein Cholesterol, HDL-C）与银屑病之间未发现稳健的因果关联。血脂次数据库的单变量孟德尔随机化分析结果与主数据库一致。反向孟德尔随机化分析显示，银屑病与LDL-C（β=-0.009，95%CI=-0.016~-0.002，p=0.009）、HDL-C（β=-0.011，95%CI=-0.021~-0.002，p=0.016）存在因果关联，但银屑病与TG之间的反向因果分析结果未达到统计学显著性。基于血脂主数据库的多变量孟德尔随机化分析结果显示，LDL-C（阶段1：OR=1.05，95%CI=0.99~1.25，p=0.396；阶段2：OR=1.07，95%CI=1.01~1.14，p=0.017；阶段3：OR=1.08，95%CI=1.02~1.15，p=0.012）与TG（阶段1：OR=1.11，95%CI=1.01~1.22，p=0.036；阶段2：OR=1.09，95%CI=1.03~1.15，p=0.002；阶段3：OR=1.07，95%CI=1.01~1.13，p=0.015）与银屑病呈正相关，而HDL-C与银屑病无显著关联。次分析结果与主分析结果一致。
【结论】孟德尔随机化（Mendelian Randomization, MR）研究结果为银屑病与血脂之间的因果关联提供了遗传学证据。临床中对银屑病患者进行血脂水平监测与调控，或可为其诊疗管理提供参考价值。