Objectives To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility. Methods A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1,506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analyzed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry. A total of 26 774 individuals (9,310 SLE cases and 17 464 controls) were included in this study. Results Meta-analysis on four Chinese cohorts identifies KLF2 as a novel locus associated with SLE (rs2362475; OR = 0.85, P = 2.00E-09). KLF2 is likely an Asian-specific locus as no evidence of association was detected in the four European cohorts (OR = 0.98, p = 0.58), with evidence of heterogeneity (p = 0.0019) between the two ancestral groups. Meta-analyses of results from both Chinese and Europeans identify STAB2 (rs10082873; OR = 0.89, P = 4.08E-08) and DOT1L (rs4807205; OR = 1.12, P = 8.17E-09) as trans-ancestral association loci, surpassing the genome-wide significance. Conclusions We identified three loci associated with SLE, with KLF2 a likely Chinese-specific locus, highlighting the importance of studying diverse populations in SLE genetics. We hypothesize that DOT1L and KLF2 are plausible SLE treatment targets, with inhibitors of DOT1L and inducers of KLF2 already available clinically.

Prostate cancer (PCa) is the most prevalent cancer among males and the survival period of PCa has been significantly extended. However, the probability of suffering from second primary malignancies (SPMs) has also increased. Therefore, we downloaded SPM samples from the SEER database and then retrospectively analyzed the general characteristics of 34,891 PCa patients diagnosed between 2000 and 2016. After excluding cases with unknown clinical information, 2203 patients were used to construct and validate the overall survival (OS) nomogram of SPM patients after PCa. We found that approximately 3.69% of PCa patients were subsequently diagnosed with SPMs. In addition, the three most prevalent sites of SPM were respiratory and intrathoracic organs, skin, and hematopoietic system. The top three histological types of SPMs were squamous cell carcinoma, adenoma and adenocarcinoma, nevi and melanoma. Through univariate and multivariate Cox regression analysis, we found that the site of SPM, age, TNM stage, SPM surgery history, and PCa stage were associated with the OS of SPM. By virtue of these factors, we constructed a nomogram to predict the OS of SPM. The C-index in the training set and validation set were 0.824 (95CI, 0.806–0.842) and 0.862 (95CI, 0.840–0.884), respectively. Furthermore, we plotted the receiver operating characteristic curve (ROC) and the area under curve (AUC) which showed that our model performed well in assessing the 3-year (0.861 and 0.887) and 5-year (0.837 and 0.842) OS of SPMs in the training and validation set. In summary, we investigated the general characteristics of SPMs and constructed a nomogram to predict the prognosis of SPM following PCa.

Objective Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with differences in prevalence and severity among ancestral groups. This study was undertaken to identify novel genetic components, either shared by or distinct between Asian and European populations. Methods Both trans‐ancestral and ancestry‐specific meta‐analyses of genome‐wide association studies (GWAS) for SLE were performed, involving 30,604 participants of European, Chinese, or Thai origin. Using public epigenomic data and expression quantitative trait loci, fine‐mapping analyses were conducted to identify putative causal variants and genes for the newly identified loci. Performance of polygenic risk scores for the Thai cohort was evaluated by comparing different training data. Results A 1‐bp deletion upstream of IFNLR1 was found to be associated with SLE, with the risk allele correlated with increased expression of IFNLR1. This gene encodes interferon‐λ (IFNλ) receptor 1, providing evidence of a role of type III IFN signaling in SLE. An intronic variant in SLC29A3 was found to be associated with SLE in Asians only. The putative risk variant may modulate SLC29A3 expression in a monocyte‐specific manner. SLC29A3 encodes a lysosomal nucleoside transporter, and subsequent analyses suggested that reduced lysosomal function and phagocytosis might be the mechanism underlying this association. Ancestry‐shared loci in or near TAOK3, CHD9, CAMK1D, ATXN1, and TARBP1 and Asian‐specific loci close to PEX2, FCHSD2, and TMEM116 also reached the genome‐wide significant association with SLE. In addition, trans‐ancestral meta‐analysis was shown to be valuable in risk prediction for individuals without ancestry‐matched data. Conclusion In this study both shared and Asian‐specific loci for SLE were identified, and functional annotation provided evidence of the involvement of increased type III IFN signaling and reduced lysosomal function in SLE.