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Objective Previous genome-wide association studies (GWAS), which were mainly based on single-variant analysis, have identified many systemic lupus erythematosus (SLE) susceptibility loci. However, the genetic architecture of this complex disease is far from being understood. The aim of this study was to investigate whether using a gene-based analysis may help to identify novel loci, by considering global evidence of association from a gene or a genomic region rather than focusing on evidence for individual variants. Methods Based on the results of a meta-analysis of 2 GWAS of SLE conducted in 2 Asian cohorts, we performed an in-depth gene-based analysis followed by replication in a total of 4,626 patients and 7,466 control subjects of Asian ancestry. Differential allelic expression was measured by pyrosequencing. Results More than one-half of the reported SLE susceptibility loci showed evidence of independent effects, and this finding is important for understanding the mechanisms of association and explaining disease heritability. ANXA6 was detected as a novel SLE susceptibility gene, with several single-nucleotide polymorphisms (SNPs) contributing independently to the association with disease. The risk allele of rs11960458 correlated significantly with increased expression of ANXA6 in peripheral blood mononuclear cells from heterozygous healthy control subjects. Several other associated SNPs may also regulate ANXA6 expression, according to data obtained from public databases. Higher expression of ANXA6 in patients with SLE was also reported previously. Conclusion Our study demonstrated the merit of using gene-based analysis to identify novel susceptibility loci, especially those with independent effects, and also demonstrated the widespread presence of loci with independent effects in SLE susceptibility genes. [ABSTRACT FROM AUTHOR]

Background: Androgenetic alopecia (AGA) is a well-characterized type of progressive hair loss commonly seen in men, with different prevalences in different ethnic populations. It is generally considered to be a polygenic heritable trait. Several susceptibility genes/loci, such as AR/EDA2R, HDAC9 and 20p11, have been identified as being involved in its development in European populations. In this study, we aim to validate whether these loci are also associated with AGA in the Chinese Han population. Methods: We genotyped 16 previously reported single nucleotide polymorphisms (SNPs) with 445 AGA cases and 546 healthy controls using the Sequenom iPlex platform. The trend test was used to evaluate the association between these loci and AGA in the Chinese Han population. Conservatively accounting for multiple testing by the Bonferroni correction, the threshold for statistical significance was P ≤3.13×10−3. Results: We identified that 5 SNPs at 20p11 were significantly associated with AGA in the Chinese Han population (1.84×10−11≤P≤2.10×10−6). Conclusions: This study validated, for the first time, that 20p11 also confers risk for AGA in the Chinese Han population and implicated the potential common genetic factors for AGA shared by both Chinese and European populations. [ABSTRACT FROM AUTHOR]

Background Chromosomal region 16p13 has been reported to harbour variants associated with several autoimmune diseases, including type I diabetes, rheumatoid arthritis and multiple sclerosis. Objective To test whether variants in the 16p13 region are also associated with systemic lupus erythematosus (SLE) by performing a candidate locus study in the Chinese Han population. Methods Tag single nucleotide polymorphisms (SNPs) encompassing 50 kb upstream and downstream of the 250 kb linkage disequilibrium block, previously implicated in several autoimmune diseases, were analysed in 1047 patients with SLE and 1205 controls. The SNP showing the strongest association with SLE was then replicated in an independent cohort of 1643 cases and 5930 controls. Results and conclusions The association between SNP rs12599402 and SLE reached the genome-wide significance level (p<5 × 10). The SNP was likely to tag the same functional variant as previously reported in European populations. The results suggested that the chromosomal region at 16p13 contains common susceptibility genes for different immune-mediated disorders. [ABSTRACT FROM PUBLISHER]

Vitiligo is an immune-related disease with patchy depigmentation of skin and hair caused by selective destruction of melanocytes. In recent decades, many studies have shown the association between vitiligo and HLA genes; however, the results of Han Chinese are scarce. In this study, we performed a fine-mapping analysis of the MHC region in 2818 Han Chinese subjects through a widely used HLA imputation method with a newly built large-scale Han-MHC reference panel. Three new four-digit HLA alleles ( HLA-DQB1  ∗  02:02 , HLA-DQA1  ∗  02:01 and HLA-DPB1  ∗  17:01 ) were identified to be associated with the risk of vitiligo, and four previously reported alleles were confirmed. Further conditional analysis revealed that two important variants, HLA-DQβ1 amino acid position 135 (OR = 1.79, P  = 1.87 × 10 −11 ) and HLA-B amino acid positions 45–46 (OR = 1.44, P  = 5.61 × 10 −11 ), conferred most of the MHC associations. Three-dimension ribbon models showed that the former is located within the β2 domain of the HLA-DQβ1 molecule, and the latter lies in the α1 domain of the HLA-B molecule, while both are involved in specific antigen presenting process. Finally, we summarized all significant signals in the MHC region to clarify their complex relationships, and 8.60% of phenotypic variance could be explained based on all reported variants in Han Chinese so far. Our findings highlight the complex genetic architecture of the MHC region for vitiligo in Han Chinese population and expand our understanding of the roles of HLA coding variants in the etiology of vitiligo. [ABSTRACT FROM AUTHOR]

High myopia, which is extremely prevalent in the Chinese population, is one of the leading causes of blindness in the world. Genetic factors play a critical role in the development of the condition. To identify the genetic variants associated with high myopia in the Han Chinese, we conducted a genome-wide association study (GWAS) of 493,947 SNPs in 1088 individuals (419 cases and 669 controls) from a Han Chinese cohort and followed up on signals that were associated with p < 1.0 × 10−4 in three independent cohorts (combined, 2803 cases and 5642 controls). We identified a significant association between high myopia and a variant at 13q12.12 (rs9318086, combined p = 1.91 × 10−16, heterozygous odds ratio = 1.32, and homozygous odds ratio = 1.64). Furthermore, five additional SNPs (rs9510902, rs3794338, rs1886970, rs7325450, and rs7331047) in the same linkage disequilibrium (LD) block with rs9318086 also proved to be significantly associated with high myopia in the Han Chinese population; p values ranged from 5.46 × 10−11 to 6.16 × 10−16. This associated locus contains three genes—MIPEP, C1QTNF9B-AS1, and C1QTNF9B. MIPEP and C1QTNF9B were found to be expressed in the retina and retinal pigment epithelium (RPE) and are more likely than C1QTNF9B-AS1 to be associated with high myopia given the evidence of retinal signaling that controls eye growth. Our results suggest that the variants at 13q12.12 are associated with high myopia. [Copyright &y& Elsevier]