We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.
We are grateful to all patients and their parents for participation in this study. We thank Petra Badorf and Daniela Hemmeter for excellent technical assistance. We acknowledge Klaus Griewank for critically reviewing the manuscript. The study was partly supported by a grant from the German Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung (BMBF); project ANCYLOSS, TP5).
Leptin levels are higher in patients with psoriasis compared with those in controls. Future studies are warranted to clarify the association between leptin levels and the pathomechanism of psoriasis.
Psoriasis is one of the most common dermatological disorders. The association between alcohol consumption and psoriasis has been inconsistent among studies. To examine the magnitude of the risk of developing psoriasis for drinking populations compared to those with non-drinking, and to determine causes of the variation in odds ratios (OR) between various case-control studies, we performed a comprehensive published work search and a meta-analysis of case-control studies considering prevalence. We did electronic searches on Medline, and searched reports to identify case-control studies of prevalent of psoriasis. We did meta-analyses of study-specific incremental estimates to determine the risk of psoriasis associated with drinking. The magnitude of the OR was analyzed by combining 15 case-control studies that matched defined criteria. The variance in OR between studies was explored. The overall OR of psoriasis for drinking persons compared to those with non-drinking was 1.531 (95% confidence interval [CI] = 1.164-2.014, P = 0.002) and the association remains statistically significant across a number of stratified analyses in European descent subgroup (OR = 1.432, 95% CI = 1.085-1.889, P = 0.011) and also persists in sensitivity analyses performed to assess the potential effect of varying psoriasis outcome definitions. Alcohol consumption is associated with increased risk of psoriasis. These epidemiological observations should inform the exploration of biological mechanisms that link alcohol consumption with psoriasis.
Interleukin 12 (IL-12) is a key player in model systems of autoimmunity. One of the most robust genetic findings is the association of variants in the IL12B gene with psoriasis and psoriatic arthritis (PsA). This study aims to assess whether combined evidence shows the association between IL12B polymorphisms and the susceptibility to psoriasis/PsA. We conducted a systematic review to examine the association between the IL12B rs3212227 (1188A > C) and rs6887695 and psoriasis/PsA. In addition, we used studies for which combined information from all genotypes was available to compare risks in dominant and recessive model. Potential publication bias was evaluated by Egger's linear regression test. Eleven articles met the inclusion criteria and contributed data to the meta-analyses. For rs3212227, the odds ratios the minor allele for psoriasis and PsA were 0.688 (95 % CI 0.650-0.729) and 0.707 (95 % CI 0.628-0.797), respectively. Then, for rs6887695, the pooled ORs were 0.704 (95 % CI 0.670-0.739) for psoriasis and 0.677 (95 % CI 0.599-0.767) for PsA. The overall ORs for all genotypes of rs3212227 and rs6887695 were all significantly associated with psoriasis. No publication bias was presented. Taken together, our results demonstrate a significant association between IL12B gene polymorphisms and psoriasis and PsA.
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