Kisiel Bartłomiej, Kisiel Katarzyna, Szymański Konrad, Mackiewicz Wojciech, Biało-Wójcicka Ewelina, Uczniak Sebastian, Fogtman Anna, Iwanicka-Nowicka Roksana, Koblowska Marta, Kossowska Helena, Placha Grzegorz, Sykulski Maciej, Bachta Artur, Tłustochowicz Witold, Płoski Rafał, Kaszuba Andrzej
Department of Internal Diseases and Rheumatology, Military Institute of Medicine, ul. Szaserów 128, Warszawa, Poland.
Department of Dermatology, Pediatric and Oncologic Dermatology, Medical University of Łódź, ul. Kniaziewicza 1/5, Łódź, Poland.
PLoS One. 2017 Jun 15;12(6):e0179348. doi: 10.1371/journal.pone.0179348. eCollection 2017.
To confirm the association of previously discovered psoriasis (Ps) risk loci with the disease in a Polish population and to create predictive models based on the combination of these single nucleotide polymorphisms (SNPs).
Thirty-eight SNPs were genotyped in 480 Ps patients and 490 controls. Alleles distributions were compared between patients and controls, as well as between different Ps sub-phenotypes. The genetic risk score (GRS) was calculated to assess the cumulative risk conferred by multiple loci.
We confirmed associations of several loci with Ps: HLA-C, REL, IL12B, TRIM39/RPP21, POU5F1, MICA. The analysis of ROC curves showed that GRS combining 16 SNPs at least nominally (uncorrected P<0.05) associated with Ps (GRS-N) had significantly better discriminative power than GRS combining SNPs associated with Ps after the Bonferroni correction (AUC 0.776 vs. 0.750, P = 1 x 10-4) or HLA-C (AUC 0.776 vs. 0.694, P<1 x 10-5). On the other hand, adding additional SNPs to the model did not improve its discriminatory ability (AUC 0.782 for GRS combining all SNPs, P>0.05). In order to assess the total risk conferred by GRS-N, we calculated ORs according to GRS-N quartile - the Ps OR for top vs. bottom GRS-N quartiles was 12.29 (P<1 x 10-6). The analysis of different Ps sub-phenotypes showed an association of GRS-N with age of onset and family history of Ps.
We confirmed the association of Ps with several previously identified genetic risk factors in a Polish population. We found that a GRS combining 16 SNPs at least nominally associated with Ps had a significantly better discriminatory ability than HLA-C or GRS combining SNPs associated with Ps after the Bonferroni correction. In contrast, adding additional SNPs to GRS did not increase significantly the discriminative power.
在波兰人群中证实先前发现的银屑病（Ps）风险位点与该疾病的关联，并基于这些单核苷酸多态性（SNP）的组合创建预测模型。
对480例Ps患者和490例对照进行38个SNP的基因分型。比较患者与对照之间以及不同Ps亚表型之间的等位基因分布。计算遗传风险评分（GRS）以评估多个位点赋予的累积风险。
我们证实了几个位点与Ps的关联：HLA-C、REL、IL12B、TRIM39/RPP21、POU5F1、MICA。ROC曲线分析表明，结合至少名义上（未校正P<0.05）与Ps相关的16个SNP的GRS（GRS-N）比结合经Bonferroni校正后与Ps相关的SNP的GRS具有显著更好的判别能力（AUC 0.776对0.750，P = 1×10-4）或HLA-C（AUC 0.776对0.694，P<1×10-5）。另一方面，向模型中添加额外的SNP并未提高其判别能力（结合所有SNP的GRS的AUC为0.782，P>0.05）。为了评估GRS-N赋予的总风险，我们根据GRS-N四分位数计算比值比 - 最高与最低GRS-N四分位数的Ps比值比为12.29（P<1×10-6）。对不同Ps亚表型的分析表明GRS-N与发病年龄和Ps家族史相关。
我们在波兰人群中证实了Ps与几个先前确定的遗传风险因素的关联。我们发现，结合至少名义上与Ps相关的16个SNP的GRS比HLA-C或结合经Bonferroni校正后与Ps相关的SNP的GRS具有显著更好的判别能力。相比之下，向GRS中添加额外的SNP并未显著增加判别能力。
