School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough LE11 3TU, UK.
Rheumatology, University Hospitals of Leicester NHS Trust, Leicester LE1 5WW, UK.
Genes (Basel). 2024 Aug 1;15(8):1009. doi: 10.3390/genes15081009.
Rheumatoid arthritis (RA) is a complex autoimmune disease that negatively affects synovial joints, leading to the deterioration of movement and mobility of patients. This chronic disease is considered to have a strong genetic inheritance, with genome-wide association studies (GWAS) highlighting many genetic loci associated with the disease. Moreover, numerous confounding and non-genetic factors also contribute to the risk of the disease.
This study investigates the association of selected genetic polymorphisms with rheumatoid arthritis risk and develops a polygenic risk score (PRS) based on selected genes.
A case-control study recruited fully consenting participants from the East Midlands region of the UK. DNA samples were genotyped for a range of polymorphisms and genetic associations were calculated under several inheritance models. PRS was calculated at crude (unweighted) and weighted levels, and its associations with clinical parameters were determined.
There were significant associations with the risk of RA at six genetic markers and their associated risk alleles (*G, *A, *T, *G, *A, and *T). The TTG haplotype at the VDR locus increased the risk of RA with an OR of 3.05 (CI 1.33-6.98, = 0.009). The GA haplotype of -α-308 was a significant contributor to the risk of RA in this population (OR = 2.77, CI 1.23-6.28, = 0.01), although linkage disequilibrium was low. The polygenic risk score was significantly higher in cases over controls in both unweighted (mean difference = 1.48, t = 5.387, < 0.001) and weighted (mean difference = 2.75, t = 6.437, < 0.001) results.
Several genetic loci contribute to the increased risk of RA in the British White sample. The PRS is significantly higher in those with RA and can be used for clinical applications and personalised prevention of disease.
类风湿关节炎（RA）是一种复杂的自身免疫性疾病，会对滑膜关节造成负面影响，导致患者运动和活动能力下降。这种慢性疾病被认为具有很强的遗传遗传，全基因组关联研究（GWAS）强调了许多与疾病相关的遗传位点。此外，许多混杂和非遗传因素也会增加患病风险。
本研究调查了选定的遗传多态性与类风湿关节炎风险的关联，并基于选定的基因开发了多基因风险评分（PRS）。
一项病例对照研究从英国东米德兰兹地区招募了完全同意的参与者。对一系列多态性进行 DNA 分型，并在几种遗传模型下计算遗传关联。在未加权（未加权）和加权水平计算 PRS，并确定其与临床参数的关联。
在六个遗传标记物及其相关风险等位基因（*G、*A、*T、*G、A 和T）上与 RA 风险存在显著关联。VDR 基因座的 TTG 单倍型增加了 RA 的风险，OR 值为 3.05（CI 1.33-6.98， = 0.009）。-α-308 的 GA 单倍型是该人群中 RA 发病的重要因素（OR = 2.77，CI 1.23-6.28， = 0.01），尽管连锁不平衡程度较低。在未加权（平均值差异= 1.48，t = 5.387， < 0.001）和加权（平均值差异= 2.75，t = 6.437， < 0.001）结果中，病例组的多基因风险评分均明显高于对照组。
在英国白人样本中，多个遗传位点增加了 RA 的患病风险。RA 患者的 PRS 明显更高，可用于临床应用和疾病的个体化预防。
