Xue-Jun Zhang

Anhui Medical University, Luchow, Anhui Sheng, China

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Publications (128)923.1 Total impact

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    ABSTRACT: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease that affects mainly females. What role the X chromosome plays in the disease has always been an intriguing question. In this study, we examined the genetic variants on the X chromosome through meta-analysis of two genome-wide association studies (GWAS) on SLE on Chinese Han populations. Prominent association signals from the meta-analysis were replicated in four additional Asian cohorts, with a total of 5, 373 cases and 9, 166 matched controls. We identified a novel variant in PRPS2 on Xp22.3 as associated with SLE with genome-wide significance (rs7062536, OR=0.84, P=1.00E-08). Association of the L1CAM-MECP2 region with SLE was reported previously. In this study, we identified independent contributors in this region in NAA10 (rs2071128, OR=0.81, P=2.19E-13) and TMEM187 (rs17422, OR =0.75, P= 1.47E-15), in addition to replicating the association from IRAK1-MECP2 region (rs1059702, OR=0.71, P=2.40E-18) in Asian cohorts. The X-linked susceptibility variants showed higher effect size in males than in females, similar to results from a genome-wide survey of associated SNPs on the autosomes. These results suggest that susceptibility genes identified on the X chromosome, while contributing to disease predisposition, might not contribute significantly to the female predominance of this prototype autoimmune disease.
    Human Molecular Genetics 08/2014; · 7.69 Impact Factor
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    ABSTRACT: We conducted a joint (pooled) analysis of three genome-wide association studies (GWAS) of esophageal squamous cell carcinoma (ESCC) in individuals of Chinese ancestry (5,337 ESCC cases and 5,787 controls) with 9,654 ESCC cases and 10,058 controls for follow-up. In a logistic regression model adjusted for age, sex, study and two eigenvectors, two new loci achieved genome-wide significance, marked by rs7447927 at 5q31.2 (per-allele odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.82-0.88; P = 7.72 × 10(-20)) and rs1642764 at 17p13.1 (per-allele OR = 0.88, 95% CI = 0.85-0.91; P = 3.10 × 10(-13)). rs7447927 is a synonymous SNP in TMEM173, and rs1642764 is an intronic SNP in ATP1B2, near TP53. Furthermore, a locus in the HLA class II region at 6p21.32 (rs35597309) achieved genome-wide significance in the two populations at highest risk for ESSC (OR = 1.33, 95% CI = 1.22-1.46; P = 1.99 × 10(-10)). Our joint analysis identifies new ESCC susceptibility loci overall as well as a new locus unique to the population in the Taihang Mountain region at high risk of ESCC.
    Nature genetics. 08/2014;
  • The Journal of Dermatology 05/2014; 41(5):456-7. · 2.35 Impact Factor
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    Annals of Dermatology 02/2014; 26(1):111-3. · 0.61 Impact Factor
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    ABSTRACT: Severe acne is a chronic inflammatory skin disorder characterized by widespread inflammatory lesions including nodules, cysts and potential scarring. Here we perform the first genome-wide association study of severe acne in a Chinese Han population comprising 1,056 cases and 1,056 controls using the Illumina HumanOmniZhongHua-8 BeadChip. In an independent cohort of 1,860 cases and 3,660 controls of Chinese Han, we replicate 101 SNPs of which 3 showed consistent association. We identify two new susceptibility loci at 11p11.2 (DDB2, rs747650, Pcombined=4.41 × 10(-9) and rs1060573, Pcombined=1.28 × 10(-8)) and 1q24.2 (SELL, rs7531806, Pcombined=1.20 × 10(-8)) that are involved in androgen metabolism, inflammation processes and scar formation in severe acne. These results point to new genetic susceptibility factors and suggest several new biological pathways related to severe acne.
    Nature Communications 01/2014; 5:2870. · 10.74 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate whether risk of gastric cancer (GC) was associated with single nucleotide polymorphisms (SNPs) in a gene cluster on the chromosome 17q12-q21 (ERBB2 amplicon) in the Chinese Han population. We detected twenty-six SNPs in this gene cluster containing START domain containing 3 (STARD3), protein phosphatase 1 regulatory subunit 1B (PPP1R1B/DARPP32), titin-cap (TCAP), per1-like domain containing 1(PERLD1/CAB2), human epidermal growth factor receptor-2 (ERBB2/HER2), zinc-finger protein subfamily 1A 3 (ZNFN1A3/IKZF3) and DNA topoisomerase 2-alpha (TOP2A) genes in 311 patients with GC and in 425 controls by Sequenom. We found no associations between genetic variations and GC risk. However, hapolotype analysis implied that the haplotype CCCT of STARD3 (rs9972882, rs881844, rs11869286 and rs1877031) conferred a protective effect on the susceptibility to GC (P=0.043, odds ratio [OR]=0.805, 95% confidence intervals [95%CI]=0.643-0.992). The STARD3 rs1877031 TC genotype endued histogenesis of gastric mucinous adenocarcinoma and signet-ring cell carcinoma (P=0.021, OR=2.882, 95%CI=1.173-7.084). We examined the expression of STARD3 in 243 tumor tissues out of the 311 GC patients and 20 adjacent normal gastric tissues using immumohistochemical (IHC) analysis and tissue microarrays (TMA). Expression of STARD3 was observed in the gastric parietal cells and in gastric tumor tissues and significantly correlated with gender (P=0.004), alcohol drinking (P<0.001), tumor location (P=0.007), histological type (P=0.005) and differentiation (P=0.023) in GC. We concluded that the combined effect of haplotype CCCT of STARD3 might affect GC susceptibility. STARD3 expression might be related to the tumorigenesis of GC in the Chinese population.
    Gene 11/2013; · 2.20 Impact Factor
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    Annals of Dermatology 11/2013; 25(4):508-10. · 0.61 Impact Factor
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    ABSTRACT: Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.
    Rheumatology International 10/2013; · 2.21 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWASs) have revealed a large number of genetic risk loci for many autoimmune diseases. One clear finding emerging from the published genetic studies of autoimmunity is that different autoimmune diseases, such as psoriasis and systemic lupus erythematosus (SLE), share susceptibility loci. Our study explores additional susceptibility loci shared by psoriasis and SLE in the Chinese Han population. In total, 20 single nucleotide polymorphisms (SNPs) in 17 previously reported psoriasis susceptibility loci and 34 SNPs from 24 previously reported SLE susceptibility loci were investigated in our initial psoriasis and SLE GWAS dataset. Among these SNPs, we selected two SNPs (rs8016947 and rs4649203) with association values of p<5×10(-2) for both diseases in the GWAS data for further investigation in psoriasis (7260 cases and 9842 controls) and SLE (2207 cases and 9842 controls) using a Sequenom MassARRAY system. We found that these two SNPs (rs8016947 and rs4649203) in two loci (NFKBIA and IL28RA) were associated with psoriasis and SLE with genome-wide significance (Pcombined<5×10(-8) in psoriasis and Pcombined<5×10(-8) in SLE): rs8016947 at NFKBIA (Pcombined-psoriasis=3.90×10(-10), Pcombined-SLE=1.08×10(-13)) and rs4649203 at IL28RA (Pcombined-psoriasis=3.91×10(-12), Pcombined-SLE=9.90×10(-9)). These results showed that two common susceptibility loci (NFKBIA and IL28RA) are shared by psoriasis and SLE in the Chinese Han population.
    Journal of Medical Genetics 09/2013; · 5.70 Impact Factor
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    ABSTRACT: SLE has a complex etiology and is affected by both genetic and environmental factors. Although more than 40 loci have shown robust association with SLE, the details in these loci, such as the independent contributors and the genes involved, are still unclear. In this study, we performed meta-analysis of two existing GWASs on Chinese Han populations from Hong Kong and Anhui, China, and followed the findings by further replication on three additional Chinese and Thailand cohorts with a total of 4,254 cases and 6, 262 controls matched geographically and ethnically. We discovered multiple susceptibility variants for SLE in the 11q23.3 region, including variants in/near PHLDB1 (rs11603023, P_combined=1.25E-08, OR=1.20), DDX6 (rs638893, P_combined=5.19E-07, OR=1.22) and CXCR5 (rs10892301, P_combined=2.51E-08, OR=0.85). Genetic contributions from the newly identified variants were all independent of SNP rs4639966, whose association was reported from the previous GWAS. In addition, the three newly identified variants all showed independent association with the disease through modeling by both stepwise and conditional logistic regression. The presence of multiple independent variants in this region emphasizes its role in SLE susceptibility, and also hints the possibility that distinct biological mechanisms might be involved in the disease involving this genomic region.
    Human Molecular Genetics 09/2013; · 7.69 Impact Factor
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    ABSTRACT: Single-nucleotide polymorphisms (SNPs) of adiponectin (ADIPOQ), adiponectin receptor 1 (ADIPOR1) and ADIPOR2 genes contribute to the risk and progression of cancers. Here, we investigated the associations between variants of these three genes and the risk of gastric cancer. We genotyped six ADIPOQ SNPs, nine ADIPOR1 SNPs and six ADIPOR2 SNPs using the Sequenom technique in a hospital-based case-control study of patients with gastric cancer and cancer-free controls in the Chinese Han population. We found associations of certain variants with location of gastric cancer. Rs16861205 with the minor allele A in ADIPOQ, rs10773989 with the minor allele C and rs1044471 with the minor allele T in ADIPOR2 presented significant associations with a decreased risk of cardia cancer (P = 0.024, OR 0.605, 95 % CI 0.390-0.938; P = 0.015, OR 0.699, 95 % CI 0.522-0.935; and P = 0.022, OR = 0.703, 95 % CI 0.519-0.951, respectively). ADIPOQ rs16861205 with minor allele A displayed an association with an increased risk of body cancer (P = 0.010, OR 1.821, 95 % CI 1.148-2.890). Further stratified analysis of the patients indicated that there were significant correlations for rs1342387A/G (P = 0.027) and rs16861205A/G (P = 0.000) with tumor location; rs16850799A/G (P = 0.004) and rs2058033C/A (P = 0.003) with invasion depth; rs16850799A/G (P = 0.019) with the tumor-node-metastasis stage; rs16850799A/G (P = 0.016), rs1501299A/C (P = 0.005) and rs1063538C/T (P = 0.017) with alcohol consumption; rs11612414A/G (P = 0.040) and rs12733285T/C (P = 0.005) with salted food; rs1063538C/T (P = 0.043) with family history of gastric cancer; and rs11612414A/G (P = 0.029) with gender. Adiponectin expression significantly correlated with gender (P = 0.014), alcohol consumption (P = 0.037), family history (P = 0.019) and invasion depth of primary tumor (P = 0.024). Our data suggested that variants of ADIPOQ may be genetic markers conferring susceptibility to gastric cancer subtypes. These findings need to be validated in a larger panel of samples from distinct populations.
    Medical Oncology 09/2013; 30(3):658. · 2.14 Impact Factor
  • Chinese medical journal 09/2013; 126(18):3591. · 0.90 Impact Factor
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    ABSTRACT: Psoriasis is a chronic inflammatory disease with a complex genetic architecture. To further advance gene discovery, we extended our GWAS dataset of 1,139 cases and 2,234 controls and replicated two independent cohorts of 7,200 cases and 10,491 controls. We identified the missense variant rs2303138 (p.Ala763Thr) within the LNPEP gene associated with psoriasis (Pcombined=1.83 × 10(-13), OR=1.16) and validated 4 previously reported genes: IL28RA, NFKBIA, TRAF3IP2 and CARD14 (9.74 × 10(-11)P9.37 × 10(-5)), which confirmed the involvement of the NF-κB signaling pathway in psoriasis pathogenesis. LNPEP, also named insulin-responsive aminopeptidase, was identified as a angiotensin IV receptor. Protein function prediction suggested that this missense variant of LNPEP was most likely deleterious. Expression analysis showed that LNPEP was significantly down-regulated in psoriatic lesions compared to control skin (P=1.44 × 10(-6)) and uninvolved patient skin (P=2.95 × 10(-4)). Pathway analysis indicated that LNPEP was involved in the renin-angiotensin system, which also plays a key role in cardiovascular disease and diabetes. These results provided genetic evidence that psoriasis might share common mechanisms with hypertension and diabetes, which was consistent with clinical observations. Our study identified a genetic susceptibility factor and provided genetic evidence of insight into the psoriasis pathogenesis with the involvement of renin-angiotensin system pathway.Journal of Investigative Dermatology accepted article preview online, 29 July 2013. doi:10.1038/jid.2013.317.
    Journal of Investigative Dermatology 07/2013; · 6.19 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) identified several genetic risk factors for breast cancer, however, most of them were validated among women of European ancestry. This study examined single-nucleotide polymorphisms (SNPs) contributing to breast cancer in Chinese (984 cases and 2206 controls) and German (311 cases and 960 controls) populations. Eighteen SNPs significantly associated with breast cancer, previously identified in GWAS were genotyped. Twelve SNPs passed quality control and were subjected to statistical analysis. Seven SNPs were confirmed to be significantly associated with breast cancer in the Chinese population, reflecting three independent loci (ESR1, FGFR2, TOX3) and five of these were also confirmed in the German population. The strongest association was identified for rs2046210 in the Chinese (odds ratio (OR)=1.42, 95% confidence interval (CI)=1.28-1.59, P=1.9 × 10(-10)) and rs3803662 in the German population (OR=1.43, 95% CI=1.17-1.74, P=4.01 × 10(-4)), located upstream of the ESR1 and TOX3 gene, respectively. For the first time, rs3757318 at 6q25.1, located next to the gene encoding estrogen receptor α (ESR1) was found to be strongly associated with breast cancer (OR=1.33, 95% CI=1.18-1.49, P=1.94 × 10(-6)) in the Chinese population. The frequency of this variant was markedly lower in the German population and the association was not significant. Despite the genetic differences, essentially the same risk loci were identified in the Chinese and the German populations. Our study suggested the existence of common genetic factors as well as disease susceptibility differences for breast cancer in both populations and highlighted the importance of performing comparison analyses for disease susceptibility within ethnic populations.European Journal of Human Genetics advance online publication, 13 March 2013; doi:10.1038/ejhg.2013.38.
    European journal of human genetics: EJHG 03/2013; · 3.56 Impact Factor
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    ABSTRACT: BACKGROUND: Psoriasis is a common multi-factorial skin disease, in which gene-gene and gene-environment interactions may affect the onset, manifestation and clinical course. OBJECTIVE: To investigate the underlying gene-environment interaction among several established susceptibility genes, cigarette smoking and alcohol intake. METHODS: Using a two-stage case-control design, we searched for pairwise interactions between cigarette smoking and alcohol intake respectively with 9 single nucleotide polymorphisms (SNPs) at ERAP1, PTTG1, CSMD1, GJB2, SERPINB8, ZNF816A and TNIP1/ANXA6 that have been associated with risk for psoriasis in 7,223 subjects. Multiple logistic regression analysis was used for data analysis. RESULTS: Significant interactions were found for alcohol intake with rs3762999 (p=0.0257) and rs999556 (p=0.0071) at TNIP/ANXA6; and for cigarette smoking with rs7007032 (p=0.0023) and rs10088247 (p=0.0023) at CSMD1. CONCLUSION: This study provides empirical evidence for the gene-environment interactions between TNIP1/ANXA6 and alcohol use, CSMD1 and cigarette smoking, highlighting the importance of gene-environment interactions in the pathogenesis of psoriasis.
    Journal of dermatological science 03/2013; · 3.71 Impact Factor
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    ABSTRACT: The aim of the study is to explore additional susceptibility factors for systemic lupus erythematosus (SLE) in Chinese Hans. Based on our previous GWAS of SLE, we performed a multistage replication study involving 3,152 cases and 7,050 controls from China to identify additional susceptibility loci for SLE by using the Sequenom MassArray system. All Chinese Han samples used in this study were obtained from doctors through collaboration with multiple hospitals in two geographic regions (central and southern China). Single-marker association analyses were performed using logistic regression with gender as a covariate in each case-control cohort. The joint analysis of all combined samples was performed using logistic regression with gender and sample cohorts as covariates. The significant association evidence for rs906868 (OR = 1.14, 95 % CI 1.08-1.20, P (combined) = 7.71 × 10(-10)) and rs7579944 (OR = 1.13, 95 % CI 1.07-1.19, P (combined) = 5.55 × 10(-9)) was observed, which located at 2p23.1. In this region, limb bud and heart development homolog (LBH) was the only gene indicated, suggesting LBH might be a susceptibility gene for SLE, although its function was still unknown. The results indicated that the SNP rs7579944, rs906868 at 2p23.1 showed significant association with SLE. The genes LBH which located in this loci might be the predisposing genes of SLE.
    Rheumatology International 02/2013; · 2.21 Impact Factor
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    ABSTRACT: To identify genetic susceptibility loci for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Chinese population, we carried out a genome-wide association study (GWAS) in 2,514 chronic HBV carriers (1,161 HCC cases and 1,353 controls) followed by a 2-stage validation among 6 independent populations of chronic HBV carriers (4,319 cases and 4,966 controls). The joint analyses showed that HCC risk was significantly associated with two independent loci: rs7574865 at STAT4, P(meta) = 2.48 × 10(-10), odds ratio (OR) = 1.21; and rs9275319 at HLA-DQ, P(meta) = 2.72 × 10(-17), OR = 1.49. The risk allele G at rs7574865 was significantly associated with lower mRNA levels of STAT4 in both the HCC tissues and nontumor tissues of 155 individuals with HBV-related HCC (P(trend) = 0.0008 and 0.0002, respectively). We also found significantly lower mRNA expression of STAT4 in HCC tumor tissues compared with paired adjacent nontumor tissues (P = 2.33 × 10(-14)).
    Nature Genetics 12/2012; · 35.21 Impact Factor
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    ABSTRACT: Human DOC-2/DAB2 interactive protein (hDAB2IP) gene is a novel member of the Ras GTPase-activating family and has been demonstrated to be a tumor-suppressor gene that inhibits cell survival and proliferation and induces cell apoptosis. It was reported that the expression level of hDAB2IP in gastric cancer tissue was highly correlated with tumor progression, however, whether hDAB2IP genetic variants are associated with the risk of gastric cancer remains yet unknown. In this case-control study, we conducted a genetic analysis for hDAB2IP variants in 311 patients with gastric cancer and 425 controls from the Chinese Han population. We found that the SNP rs2243421 of hDAB2IP gene with the minor allele C significantly revealed strong association with decreased gastric cancer susceptibility (P=0.007, adjusted odds ratio [OR]=0.734, 95%CI=0.586-0.919). Haplotype rs2243421 and rs10985332 (HaploType: CC, P=0.012, aOR=0.760) and haplotype rs2243421 and rs555996 (HaploType: CG, P=0.034, aOR=0.788) represented the decreased risk of gastric cancer, respectively. On the contrary, rs2243421 and rs555996 showed an elevated susceptibility (HaploType: TG, p=0.010, aOR=1.320). Our results for the first time provided new insight into susceptibility factors of hDAB2IP gene variants in carcinogenesis of gastric cancer.
    Gene 12/2012; · 2.20 Impact Factor
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    ABSTRACT: PRDM9 is essential for the progression through early meiotic prophase, including double strand break repair, homologous chromosome pairing, and sex body formation during spermatogenesis. In order to evaluate the association of the PRDM9 gene variants with defective spermatogenesis in the Chinese Han population, we assessed two single nucleotide polymorphisms (SNPs) in the PRDM9 gene (rs1874165 and rs2973631) using Sequenom iplex technology in 309 cases of severely defective spermatogenesis (199 cases with non-obstructive azoospermia and 110 cases with severe oligozoospermia) and 377 controls. The allele frequencies of the SNPs were not statistically different between the study groups and the controls (P = 0.95 in rs1874165 and P = 0.80 in rs2973631, respectively). The genetic model analysis of the two SNPs indicated that these SNPs variants may not be associated with defective spermatogenesis in the Chinese Han population.
    Systems biology in reproductive medicine 11/2012; · 1.85 Impact Factor
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    ABSTRACT: Anorectal malformations (ARMs, congenital obstruction of the anal opening) are among the most common birth defects requiring surgical treatment (2-5/10,000 live-births) and carry significant chronic morbidity. ARMs present either as isolated or as part of the phenotypic spectrum of some chromosomal abnormalities or monogenic syndromes. The etiology is unknown. To assess the genetic contribution to ARMs, we investigated single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) at genome-wide scale. A total of 363 Han Chinese sporadic ARM-patients and 4,006 Han Chinese controls were included. Overall, we detected a 1.3-fold significant excess of rare-CNVs in patients. Stratification of patients by presence/absence of other congenital anomalies showed that while syndromic-ARM patients carried significantly longer rare duplications than controls (p=0.049), non-syndromic patients were enriched with both rare deletions and duplications when compared to controls (p=0.00031). Twelve chromosomal aberrations and 114 rare-CNVs were observed in patients but not in 868 controls nor 11,943 healthy individuals from the Database of Genomic Variants (DGV). Importantly, these aberrations were observed in isolated-ARM patients. Gene-based analysis revealed 79 genes interfered by CNVs in patients only. In particular, we identified a de novo DKK4 duplication. DKK4 is a member of the WNT signaling pathway which is involved in the development of the anorectal region. In mice, Wnt disruption results in ARMs. Our data suggest a role for rare-CNVs not only in syndromic but also in isolated-ARM patients and provide a list of plausible candidate genes for the disorder.
    Human Molecular Genetics 10/2012; · 7.69 Impact Factor

Publication Stats

2k Citations
923.10 Total Impact Points


  • 2002–2013
    • Anhui Medical University
      • Institute of Dermatology
      Luchow, Anhui Sheng, China
  • 2012
    • BGI Human Genome Center
      Peping, Beijing, China
  • 2011
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China
  • 2010
    • Xinxiang University
      Sinsiang-hsien, Henan Sheng, China
  • 2009
    • Shandong Academy of Sciences
      Chi-nan-shih, Shandong Sheng, China
  • 2008
    • Shanghai Institute of Microsystem And Information Technology
      Shanghai, Shanghai Shi, China
  • 2002–2006
    • Chinese National Human Genome Center at Shanghai
      Shanghai, Shanghai Shi, China