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ABSTRACT: Liver carcinomas have been classified into three types: hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and combined HCC-CC (CHC). We aim to find the common and different characteristic of these three types of liver cancer. The gene expression profiling of HCC, CC, and CHC were compared with each other, and enrichment pathways and processes in these three liver cancers were also identified. Using GSE15765 datasets downloaded from NCBI GEO database, the gene expression profiling of HCC, CC, and CHC were compared with each other (HCC compared with CC, HCC compared with CHC, and CC compared with HCC). Then, the differentially expressed genes (DEGs) were identified in these three groups respectively, and three PPI networks were constructed for DEGs in each group. Subsequently, the clusters in these networks were identified and further analyzed by ClusterONE and MCODE. Finally, gene set enrichment analysis enrichment analysis was performed to illustrate altered pathways and processes for each type of liver cancer. A total of 112, 530, and 64 DEGs were identified in three groups, respectively, and three PPI networks were constructed respectively for the corresponding group. Through the cluster analysis, we found some new differential marker genes for distinguishing the difference between these three types of liver cancer. We also indicated that we can distinguish HCC with CC through altered pathways and processes. Our findings develop new biomarkers for categorizing the primary liver cancer and may improve patient prognosis of these cancers. However, further validation is required since our results were based on microarray data derived from a small sample size.
Tumor Biology 03/2013; · 1.94 Impact Factor
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ABSTRACT: BACKGROUND: The human paraoxonase (PON) gene family has three isoforms: PON1, PON2 and PON3. These genes are implicated as potential risk factors of cerebrovascular disease and can prevent oxidative modification of low-density lipoproteins and atherosclerosis. This study evaluated the association between the genetic variants of all three PON genes and the risks of total stroke, ischemic stroke and hemorrhagic stroke in the Han Chinese population. METHODS: A total of 1016 subjects were recruited, including 508 healthy controls and 498 patients (328 with ischemic stroke and 170 with hemorrhagic stroke). A total of 11 single nucleotide polymorphisms (SNPs) covering the PON genes were genotyped for statistical analysis. Two of the 11 SNPs (rs662 and rs854560) were contextualized in a meta-analysis of ischemic stroke. RESULTS: The presence of rs705381 (-162) in the promoter region of PON1 was significantly associated with total stroke (Padjusted = 0.0007, OR = 0.57 [95% CI = 0.41-0.79]) and ischemic stroke (Padjusted = 0.0017, OR = 0.54 [95% CI = 0.37-0.79]) when analyzed using a dominant model, but was not associated with hemorrhagic stroke. There was also a nominal association between rs854571 (-824) and total stroke. Meta-analysis demonstrated a significant nominal association between rs662 and ischemic stroke, but there was no evidence of an association between rs662 and ischemic stroke risk in a single site association study. CONCLUSIONS: These findings indicate that polymorphisms of PON1 gene may be a risk factor of stroke.
BMC Medical Genetics 01/2013; 14(1):16. · 2.33 Impact Factor
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Jing Dong,
Guangfu Jin,
Chen Wu,
Huan Guo,
Baosen Zhou,
Jiachun Lv,
Daru Lu,
Yongyong Shi,
Yongqian Shu,
Lin Xu, [......],
Ying Yan,
Jibin Liu,
Christopher I Amos,
Feng Chen,
Wen Tan,
Li Jin,
Tangchun Wu,
Zhibin Hu,
Dongxin Lin,
Hongbing Shen
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ABSTRACT: Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR) = 0.78, 95% confidence interval (CI) = 0.72-0.84, P = 1.19×10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR = 0.74, 95% CI = 0.67-0.81) or 32% (OR = 0.68, 95% CI = 0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR = 0.96, 95% CI = 0.90-1.02, P = 0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.
PLoS Genetics 01/2013; 9(1):e1003190. · 8.69 Impact Factor
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ABSTRACT: To assess the association between the variant of Cytochrome P450 2A6 whole gene deletion (CYP2A6*4) polymorphism and risk of lung cancer.
Two investigators independently searched the PubMed, Elsevier, EMBASE, Web of Science, Wiley Online Library and Chinese National Knowledge Infrastructure (CNKI). Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for CYP2A6*4 and lung cancer were calculated in a fixed-effects model (the Mantel-Haenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.
This meta-analysis included seven eligible studies, which included 2524 lung cancer cases and 2258 controls (cancer-free). Overall, CYP2A6*4 was associated with the risk of lung cancer (allele*4 vs. allele non-*4, pooled OR = 0.826, 95% CI = 0.725-0.941, P-value = 0.004). When stratifying for population, significant association was observed in Asian (additive model, pooled OR = 0.794, 95% CI = 0.694-0.909, P-value = 0.001; dominant model, pooled OR = 0.827, 95% CI = 0.709-0.965, P-value = 0.016; recessive model (pooled OR = 0.444, 95% CI = 0.293-0.675, P-value <0.0001). In the overall analysis, a comparably significant decrease in the frequency of *4/*4 genotype was detected between cases and controls in Asian while no *4/*4 genotype was detected in Caucasian in collected data.
This meta-analysis suggests that the CYP2A6*4 polymorphism is associated with susceptibility of lung cancer in Asian. The whole gene deletion of CYP2A6 may decrease the risk of lung cancer in Asian samples.
PLoS ONE 01/2013; 8(4):e59556. · 4.09 Impact Factor
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Yongyong Shi,
Han Zhao,
Yuhua Shi,
Yunxia Cao,
Dongzi Yang, Zhiqiang Li,
Bo Zhang,
Xiaoyan Liang,
Tao Li,
Jianhua Chen, [......],
Dongni Zhao,
Chun-e Ren,
Xiuqing Li,
Wei Zhang,
Yiwen Zhang,
Jiangtao Zhang,
Di Wu,
Changming Zhang,
Lin He,
Zi-Jiang Chen
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ABSTRACT: Following a previous genome-wide association study (GWAS 1) including 744 cases and 895 controls, we analyzed genome-wide association data from a new cohort of Han Chinese (GWAS 2) with 1,510 polycystic ovary syndrome (PCOS) cases and 2,016 controls. We followed up significantly associated signals identified in the combined results of GWAS 1 and 2 in a total of 8,226 cases and 7,578 controls. In addition to confirming the three loci we previously reported, we identify eight new PCOS association signals at P < 5 × 10(-8): 9q22.32, 11q22.1, 12q13.2, 12q14.3, 16q12.1, 19p13.3, 20q13.2 and a second independent signal at 2p16.3 (the FSHR gene). These PCOS association signals show evidence of enrichment for candidate genes related to insulin signaling, sexual hormone function and type 2 diabetes (T2D). Other candidate genes were related to calcium signaling and endocytosis. Our findings provide new insight and direction for discovering the biological mechanisms of PCOS.
Nature Genetics 08/2012; 44(9):1020-5. · 35.53 Impact Factor
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Jing Dong,
Zhibin Hu,
Chen Wu,
Huan Guo,
Baosen Zhou,
Jiachun Lv,
Daru Lu,
Kexin Chen,
Yongyong Shi,
Minjie Chu, [......],
Yuxia Zhao,
Haibo Zhang,
Ying Yan,
Christopher I Amos,
Feng Chen,
Wen Tan,
Li Jin,
Tangchun Wu,
Dongxin Lin,
Hongbing Shen
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ABSTRACT: To find additional susceptibility loci for lung cancer, we tested promising associations from our previous genome-wide association study (GWAS) of lung cancer in the Chinese population in an extended validation sample size of 7,436 individuals with lung cancer (cases) and 7,483 controls. We found genome-wide significant (P < 5.0 × 10(-8)) evidence for three additional lung cancer susceptibility loci at 10p14 (rs1663689, close to GATA3, P = 2.84 × 10(-10)), 5q32 (rs2895680 in PPP2R2B-STK32A-DPYSL3, P = 6.60 × 10(-9)) and 20q13.2 (rs4809957 in CYP24A1, P = 1.20 × 10(-8)). We also found consistent associations for rs247008 at 5q31.1 (IL3-CSF2-P4HA2, P = 7.68 × 10(-8)) and rs9439519 at 1p36.32 (AJAP1-NPHP4, P = 3.65 × 10(-6)). Four of these loci showed evidence for interactions with smoking dose (P = 1.72 × 10(-10), P = 5.07 × 10(-3), P = 6.77 × 10(-3) and P = 4.49 × 10(-2) for rs2895680, rs4809957, rs247008 and rs9439519, respectively). These results advance our understanding of lung cancer susceptibility and highlight potential pathways that integrate genetic variants and smoking in the development of lung cancer.
Nature Genetics 07/2012; 44(8):895-9. · 35.53 Impact Factor
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Shengping Li,
Ji Qian,
Yuan Yang,
Wanting Zhao,
Juncheng Dai,
Jin-Xin Bei,
Jia Nee Foo,
Paul J McLaren, Zhiqiang Li,
Jingmin Yang, [......],
Hongbing Shen,
Lin He,
Paul I W de Bakker,
Hongyang Wang,
Yi-Xin Zeng,
Mengchao Wu,
Zhibin Hu,
Yongyong Shi,
Jianjun Liu,
Weiping Zhou
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ABSTRACT: Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV-related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV-positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV-positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×10⁻¹⁹) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×10⁻⁸), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×10⁻⁴; rs455804: OR = 0.84, P = 6.92×10⁻³). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV-related HCC, suggesting the involvement of glutamate signaling in the development of HBV-related HCC.
PLoS Genetics 07/2012; 8(7):e1002791. · 8.69 Impact Factor
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ABSTRACT: The optical response of graphene micro-structures, such as micro-ribbons and
disks, is dominated by the localized plasmon resonance in the far infrared (IR)
spectral range. An ensemble of such structures is usually involved and the
effect of the coupling between the individual structures is expected to play an
important role. In this paper, the plasmonic coupling of graphene
microstructures in different configurations is investigated. While a relatively
weak coupling between graphene disks on the same plane is observed, the
coupling between vertically stacked graphene disks is strong and a drastic
increase of the resonance frequency is demonstrated. The plasmons in a more
complex structure can be treated as the hybridization of plasmons from more
elementary structures. As an example, the plasmon resonances of graphene
micro-rings are presented, in conjunction with their response in a magnetic
field. Finally, the coupling of the plasmon and the surface polar phonons of
SiO2 substrate is demonstrated by the observation of a new hybrid resonance
peak around 500cm-1.
05/2012;
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ABSTRACT: ObjectiveBiological markers performable in routine practice and able to predict the clinical outcome of advanced non-small cell lung
cancer (NSCLC) treated with gefitinib are urgently needed.
MethodsWe analyzed EGFR / HER2 / HER3 primary tumour immunohistochemical expression in a prospective and consecutive series of 90
Chinese patients. Platinum-pretreated patients received a 250 mg oral dose of gefitinib once daily until disease progression;
EGFR / HER2 / HER3 tumour status was related with the clinical outcome in terms of response rate (RR), time to disease progression
(TTP), and overall survival (OS).
ResultsA high expression (scores 2–3) of EGFR, HER2 and HER3 was verified in 16.7%, 43.3% and 21.1% of tumors, respectively. EGFR
and HER3 status were not significantly related with response, while the HER2 overexpression result was significantly associated
with a higher RR (35.9% vs. 15.7%, P = 0.027). The RR in the 13 patients with both HER2 and HER3 expression was also significantly higher than in the other 77
patients (53.8% vs. 22.1%, P = 0.036). EGFR / HER2 / HER3 status was not significantly correlated with TTP or OS.
ConclusionThe HER2 immunohistochemical expression can play a role in the clinical management of Chinese patients with advanced NSCLC
who are candidates for gefitinib therapy.
The Chinese-German Journal of Clinical Oncology 04/2012; 7(8):440-446.
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ABSTRACT: In order to identify fractured reservoirs and determine their fracture parameters with a high definition array laterolog,
we built a fracture-induced anisotropic formation model with a parallel fracture group. The three-dimensional finite element
method is used to simulate the responses of the array laterolog, and then the primary inversion method is utilized. Numerical
simulation shows that when the fracture spacing is small, the array laterolog response of the fracture group is the same as
that of a formation with macroscopic electrical anisotropy. The apparent resistivity of the array laterolog is approximately
inversely proportional to fracture porosity. The anisotropy depends on the fracture porosity in the fractured formation, which
accordingly results in response variation of the array laterolog. The higher the fracture dip, the larger the apparent resistivity.
When the fracture dip is low the difference between the deep and shallow apparent resistivities is small, and when the dip
is high the difference turns out to be positive. The fracture parameters were inverted using the Marquardt non-linear least
squares method. The results, both fracture porosity and dip show a good match with parameters in the actual formation model.
This will promote the application of the array laterolog in evaluating fractured reservoirs.
Key wordsFracturing–anisotropic reservoir–fracture dip–fracture porosity–array laterolog
Petroleum Science 04/2012; 8(1):11-16. · 0.47 Impact Factor
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ABSTRACT: A new matrix product, called semi-tensor product of matrices, is introduced. Using this, an algebraic expression of logic
is proposed, where a logical variability is expressed as a vector, a logic function is expressed as a matrix and the function
values are obtained by the product of matrix with its arguments’ vectors. Under this framework, the problem of solving logic
equations is investigated. For a static logic equation, we convert it into a set of linear algebraic equations. Then the solution
becomes obvious. Some examples are presented to show that it is useful for logic infection.
Frontiers of Electrical and Electronic Engineering in China 04/2012; 4(3):259-269.
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Qikun Xue,
Jianlong Li,
Mu Sun,
Hua Lu,
T. Hashizume,
Y. Hasegawa,
K. Ohno, Zhiqiang Li,
Y. Kawazoe,
T. Sakurai,
H. Kamiyama,
H. Shinohara
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ABSTRACT: Scanning tunneling microscopy study revealed a van der Waals C60, solid film with 13% room-temperature lattice expansion on the GaAs(00l) 2 x 4 surface. The mechanism involves fundamental
Coulomb interaction due to charge transfer from the GaAs substrate. Theoretical calculation determines the charge transfer
to be 1.76 electrons per C60 molecule. Oriented at its (110) crystallographic axis this film also distinguishes itself from those formed on all other
semiconductor and metal substrates where only the low-energy (111) hexagonal packing of C60 molecules was developed. It is shown that this is due to the one-dimensional confinement effect of the anisotropic substrate,
which may have the prospect of controlling crystal growth.
Science in China Series A Mathematics 04/2012; 43(11):1224-1232. · 0.70 Impact Factor
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ABSTRACT: Patient motion is a common challenge in the clinical setting and fast spin echo longitudinal relaxation time fluid attenuating inversion recovery imaging method with motion correction would be highly desirable. The motion correction provided by transverse relaxation time- and diffusion-weighted periodically rotated overlapping parallel lines with enhanced reconstruction methods has seen significant clinical adoption. However, periodically rotated overlapping parallel lines with enhanced reconstruction with fast spin echo longitudinal relaxation time fluid attenuating inversion recovery-weighting has proved challenging since motion correction requires wide blades that are difficult to acquire while also maintaining short echo train lengths that are optimal for longitudinal relaxation time fluid attenuating inversion recovery-weighting. Parallel imaging provides an opportunity to increase the effective blade width for a given echo train lengths. Coil-by-coil data-driven autocalibrated parallel imaging methods provide greater robustness in the event of motion compared to techniques relying on accurate coil sensitivity maps. However, conventional internally calibrated data-driven parallel imaging methods limit the effective acceleration possible for each blade. We present a method to share a single calibration dataset over all imaging blades on a slice by slice basis using the APPEAR non-Cartesian parallel imaging method providing an effective blade width increase of 2.45×, enabling robust motion correction. Results comparing the proposed technique to conventional Cartesian and periodically rotated overlapping parallel lines with enhanced reconstruction methods demonstrate a significant improvement during subject motion and maintaining high image quality when no motion is present in normal and clinical volunteers. Magn Reson Med, 2012. © 2012 Wiley Periodicals, Inc.
Magnetic Resonance in Medicine 03/2012; · 2.96 Impact Factor
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ABSTRACT: The Motin family proteins can regulate cell polarity, cell mobility, and proliferation during embryonic development by controlling distinct signaling pathways. In this study, we demonstrate that amotl2 knockdown in zebrafish wild-type embryos results in embryonic dorsalization, and this effect can be antagonized by co-knockdown of the dorsal inducer β-catenin2. Overexpression of amotl2 in masterblind (mbl) homozygous embryos, in which canonical Wnt signaling is up-regulated due to an axin1 mutation, transforms eyeless phenotype into smaller eyes, whereas co-knockdown of amot, amotl1, and amotl2 leads to development of smaller eyes in mbl heterozygotes. In cultured mammalian cells, Motin family members all possess the ability to attenuate Wnt/β-catenin signaling. Focusing on Amotl2, we show that Amotl2 can associate with and trap β-catenin in the Rab11-positive recycling endosomes, and as a result, the amount of β-catenin in the cytosol and nucleus is reduced. Thus, our findings provide novel insights into functions of Motin family members and regulation of Wnt/β-catenin signaling.
Journal of Biological Chemistry 02/2012; 287(16):13005-15. · 4.77 Impact Factor
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Qian Zhao,
Tao Li,
Xinzhi Zhao,
Ke Huang,
Ti Wang, Zhiqiang Li,
Jue Ji,
Zhen Zeng,
Zhao Zhang,
Kan Li,
Guoyin Feng,
David St Clair,
Lin He,
Yongyong Shi
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ABSTRACT: Background:Rare copy number variations (CNVs) were involved in the etiology of neuropsychiatric disorders, and some of them appeared to be shared risk factors for several different diseases. One of those promising loci is the CNV at 15q11.2, including 4 genes, TUBGCP5, CYFIP1, NIPA2, and NIPA1. Several studies showed that microdeletions at this locus were significant associated with schizophrenia. In the current study, we investigated the role of both rare CNVs and common single nucleotide polymorphisms (SNPs) at 15q11.2 in schizophrenia in the Chinese Han population.Methods:We screened deletions at 15q11.2 in 2058 schizophrenia patients and 3275 normal controls in Chinese Han population by Affymetrix 500K/6.0 SNP arrays and SYBR green real-time polymerase chain reaction and then validated deletions by multiplex ligation-dependent probe amplification and Taqman real-time assays. We successfully genotyped 27 tag SNPs in total and tested associations in 1144 schizophrenia cases and 1144 normal controls.Results:We found a triple increase of deletions in cases over controls, with OR = 4.45 (95% CI = 1.36-14.60) and P = .014. In the analysis of common SNPs, we found that the most significant SNP in schizophrenia was rs4778334 (OR = .72, 95% CI = 0.60-0.87, allelic P = .0056 after permutation, genotypic P = .015 after permutation). We also found SNP rs1009153 in CYFIP1 was associated with schizophrenia (OR = 0.82, 95% CI = 0.73-0.93, allelic P = .044 after permutation).Conclusion:We found that both rare deletions and common variants at 15q11.2 were associated with schizophrenia in the Chinese Han population.
Schizophrenia Bulletin 02/2012; · 8.80 Impact Factor
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Yingying Qin,
Han Zhao,
Jianfeng Xu,
Yongyong Shi, Zhiqiang Li,
Jie Qiao,
Jiayin Liu,
Chunrong Qin,
Chune Ren,
Jie Li,
Shiling Chen,
Yunxia Cao,
Joe Leigh Simpson,
Zi-Jiang Chen
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ABSTRACT: Premature ovarian failure (POF) is a complex heritable disorder known to be caused by chromosomal abnormalities and to date a limited number of known mutations, often autosomal. We sought to identify additional genetic loci associated with POF by performing the first large-scale genome-wide association study (GWAS). GWAS, using Affymetrix SNP 6.0 chip, was conducted in an initial discovery set of 391 well-documented (follicle-stimulating hormone >40 IU/ml) Chinese Han POF patients, compared with 895 unrelated Chinese female controls. A replication study on the most significant loci was then performed in an independent set of 400 cases and 800 controls. Suggestive significant associations were observed at 8q22.3. Replication of eight single-nucleotide polymorphisms (SNPs) (rs10464815, rs10808365, rs3847152, rs3847153, rs3847154, rs3843552, rs10955242, rs3843555) (P ≤ 3.86 × 10(-6)) was confirmed in verification sets. No specific candidate gene was found in the immediate region of 8q22.3. This GWAS, involving by far the largest sample of POF cases accumulated to date, revealed heretofore unrecognized association between POF and a novel genetic locus or region of unknown nature on 8q22.3. We speculate existence of a long-distance regulatory region that has relevance to the control of ovarian differentiation or oogenesis. Given failure to find association with any of the other autosomal regions known to harbor genes causing ovarian failure, our findings also underscore the likelihood of considerable genetic and etiologic heterogeneity in POF and the need for additional approaches like whole-genome sequencing.
Human Molecular Genetics 01/2012; 21(2):430-6. · 7.64 Impact Factor
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Yongyong Shi,
Zhibin Hu,
Chen Wu,
Juncheng Dai,
Huizhang Li,
Jing Dong,
Meilin Wang,
Xiaoping Miao,
Yifeng Zhou,
Feng Lu, [......], Zhiqiang Li,
Minjie Chu,
Hongxia Ma,
Jiaping Chen,
Guangfu Jin,
Wen Tan,
Tangchun Wu,
Zhengdong Zhang,
Dongxin Lin,
Hongbing Shen
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ABSTRACT: Gastric cancer, including the cardia and non-cardia types, is the second leading cause of cancer-related deaths worldwide. To identify genetic risk variants for non-cardia gastric cancer, we performed a genome-wide association study in 3,279 individuals (1,006 with non-cardia gastric cancer and 2,273 controls) of Chinese descent. We replicated significant associations in an additional 6,897 subjects (3,288 with non-cardia gastric cancer and 3,609 controls). We identified two new susceptibility loci for non-cardia gastric cancer at 5p13.1 (rs13361707 in the region including PTGER4 and PRKAA1; odds ratio (OR) = 1.41; P = 7.6 × 10(-29)) and 3q13.31 (rs9841504 in ZBTB20; OR = 0.76; P = 1.7 × 10(-9)). Imputation analyses also confirmed previously reported associations of rs2294008 and rs2976392 on 8q24, rs4072037 on 1q22 and rs13042395 on 20p13 with non-cardia gastric cancer susceptibility in the Han Chinese population.
Nature Genetics 12/2011; 43(12):1215-8. · 35.53 Impact Factor
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Yongyong Shi, Zhiqiang Li,
Qi Xu,
Ti Wang,
Tao Li,
Jiawei Shen,
Fengyu Zhang,
Jianhua Chen,
Guoquan Zhou,
Weidong Ji, [......],
David St Clair,
Hreinn Stefansson,
Kari Stefansson,
Jue Ji,
Qingzhong Wang,
Wenjin Li,
Linqing Zheng,
Hairong Zhang,
Guoyin Feng,
Lin He
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[hide abstract]
ABSTRACT: Schizophrenia is a severe mental disorder affecting ∼1% of the world population, with heritability of up to 80%. To identify new common genetic risk factors, we performed a genome-wide association study (GWAS) in the Han Chinese population. The discovery sample set consisted of 3,750 individuals with schizophrenia and 6,468 healthy controls (1,578 cases and 1,592 controls from northern Han Chinese, 1,238 cases and 2,856 controls from central Han Chinese, and 934 cases and 2,020 controls from the southern Han Chinese). We further analyzed the strongest association signals in an additional independent cohort of 4,383 cases and 4,539 controls from the Han Chinese population. Meta-analysis identified common SNPs that associated with schizophrenia with genome-wide significance on 8p12 (rs16887244, P = 1.27 × 10(-10)) and 1q24.2 (rs10489202, P = 9.50 × 10(-9)). Our findings provide new insights into the pathogenesis of schizophrenia.
Nature Genetics 12/2011; 43(12):1224-7. · 35.53 Impact Factor
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Zhiqiang Li,
Jia Qu,
Xun Xu,
Xiangtian Zhou,
Haidong Zou,
Ning Wang,
Tao Li,
Xiaohan Hu,
Qian Zhao,
Peng Chen, [......],
Zangdong He,
Jue Ji,
Ti Wang,
Junyan Li,
You Li,
Jie Liu,
Zhen Zeng,
Guoyin Feng,
Lin He,
Yongyong Shi
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[hide abstract]
ABSTRACT: High-grade myopia (HM) is highly heritable, and has a high prevalence in the Han Chinese population. We carried out a genome-wide association study involving 102 HM cases suffering from retinal degeneration, and 335 controls who were free from HM and fundus diseases. Significant single-nucleotide polymorphisms were replicated in two follow-up studies: stage I involved 2628 independent cases and 9485 controls, and stage II involved a further 263 cases and 586 HM-free controls. The results were combined in a meta-analysis. Cases and controls were drawn from the Chinese Han population. A locus in an intergenic region at 4q25, within MYP11 (4q22-q27, OMIM: 609994), was found to be associated with HM (rs10034228, P(meta) = 7.70 × 10(-13), allelic odds ratio = 0.81, 95% confidence interval 0.76-0.86). There are no known genes in the region but a number of expressed sequence tags (ESTs) have been located there, one of which (BI480957) has been reported to express in the native human retinal pigment epithelium. In addition, a predicted gene was identified in this region. The gene's predicted protein sequence is highly similar to tubulin, beta 8 and beta-tubulin 4Q. Several previous studies have shown that tubulin plays an important role in eye development. Our result is compatible with a previous linkage study in the Han Chinese population (mapping in MYP11, 4q22-q27), and provides a more accurate locus for HM. Although there is insufficient evidence to indicate that expressed EST and the predicted gene play an important role in developing HM, this region merits further study as a candidate for the disease.
Human Molecular Genetics 07/2011; 20(14):2861-8. · 7.64 Impact Factor
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Zhibin Hu,
Chen Wu,
Yongyong Shi,
Huan Guo,
Xueying Zhao,
Zhihua Yin,
Lei Yang,
Juncheng Dai,
Lingmin Hu,
Wen Tan, [......],
Zhengdong Zhang,
Feng Chen,
Xinru Wang,
Li Jin,
Jiachun Lu,
Baosen Zhou,
Daru Lu,
Tangchun Wu,
Dongxin Lin,
Hongbing Shen
[show abstract]
[hide abstract]
ABSTRACT: Lung cancer is the leading cause of cancer-related deaths worldwide. To identify genetic factors that modify the risk of lung cancer in individuals of Chinese ancestry, we performed a genome-wide association scan in 5,408 subjects (2,331 individuals with lung cancer (cases) and 3,077 controls) followed by a two-stage validation among 12,722 subjects (6,313 cases and 6,409 controls). The combined analyses identified six well-replicated SNPs with independent effects and significant lung cancer associations (P < 5.0 × 10(-8)) located in TP63 (rs4488809 at 3q28, P = 7.2 × 10(-26)), TERT-CLPTM1L (rs465498 and rs2736100 at 5p15.33, P = 1.2 × 10(-20) and P = 1.0 × 10(-27), respectively), MIPEP-TNFRSF19 (rs753955 at 13q12.12, P = 1.5 × 10(-12)) and MTMR3-HORMAD2-LIF (rs17728461 and rs36600 at 22q12.2, P = 1.1 × 10(-11) and P = 6.2 × 10(-13), respectively). Two of these loci (13q12.12 and 22q12.2) were newly identified in the Chinese population. These results suggest that genetic variants in 3q28, 5p15.33, 13q12.12 and 22q12.2 may contribute to the susceptibility of lung cancer in Han Chinese.
Nature Genetics 07/2011; 43(8):792-6. · 35.53 Impact Factor
