Medical Research Council (MRC) Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom.
Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, United Kingdom.
PLoS Med. 2019 Jan 31;16(1):e1002739. doi: 10.1371/journal.pmed.1002739. eCollection 2019 Jan.
Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and psoriasis.
Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio [OR] = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.
Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.
银屑病是一种常见的炎症性皮肤病，已有研究报道其与肥胖有关。我们旨在探讨体重指数（BMI）与银屑病之间是否存在因果关系。
在对肥胖与银屑病之间关联的已发表流行病学证据进行综述后，我们使用孟德尔随机化（MR）检验 BMI 与银屑病之间是否存在因果关系。我们使用包含 97 个与 BMI 相关的单核苷酸多态性（SNP）的遗传工具作为 BMI 的替代指标（预计比测量的 BMI 受到的混杂因素影响小得多）。使用来自英国生物库（UK Biobank）和挪威北特伦德拉格健康研究（HUNT）的个体水平数据（396495 人）进行单样本 MR。使用来自已发表的 BMI 和银屑病全基因组关联研究（GWAS）的汇总水平数据（356926 人）进行双样本 MR。使用固定效应模型对单样本和双样本 MR 估计值进行荟萃分析。为了检验潜在的反向因果效应，我们使用来自最近的银屑病全基因组分析的遗传工具来检验这种皮肤病的遗传风险是否对 BMI 有因果影响。已发表的观察性研究表明，较高的 BMI 与银屑病有关。在成年人中，银屑病患者和对照组之间的 BMI 差异平均为 1.26kg/m2（95%CI 1.02-1.51），而在儿童中，BMI 差异平均为 1.55kg/m2（95%CI 1.13-1.98）。在 UK Biobank 和 HUNT 数据集也证实了这种观察性关联。总的来说，BMI 每增加 1kg/m2，患银屑病的几率就会增加 4%（meta 分析比值比 [OR] = 1.04；95%CI 1.03-1.04；P = 1.73×10(-60)）。MR 分析提供了证据表明，较高的 BMI 会使患银屑病的几率增加 9%（BMI 每增加 1 个单位，OR = 1.09（1.06-1.12）/kg/m2；P = 4.67×10(-9)）。相比之下，MR 估计值几乎没有支持银屑病遗传风险对 BMI 的可能因果效应（银屑病患病几率每增加一倍，BMI 变化 0.004kg/m2（-0.003 至 0.011））。我们研究的局限性包括患者可能对银屑病的报告不准确，以及临床医生可能的误诊。此外，研究中的队列也存在有限的种族差异。
我们的研究使用遗传变异作为 BMI 的工具变量，提供了证据表明，较高的 BMI 会导致银屑病的风险增加。这支持了针对控制体重的治疗和生活方式干预措施的优先级，以预防或治疗这种常见的皮肤疾病。需要进行机制研究以提高对这种关系的理解。
