scholarly journals Single nucleotide polymorphism within gene in NFKBIA is associated with the risks of nasopharyngeal carcinoma in Chinese Han population.

2019 ◽  
Vol 5 (suppl) ◽  
pp. 67-67
Author(s):  
Hanyi Zhang ◽  
Shun Lu ◽  
Chang Sun ◽  
Siyao Deng ◽  
Jin Yi Lang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Association Studies ◽  
Sample Size Calculation ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Significance Level ◽  
Genotype Frequencies ◽  
Increased Risk

67 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs (Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs that we found were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.

Association of single nucleotide polymorphisms within genes in NF-κB, TGF-β, and JNK signaling pathways with the risks of nasopharyngeal carcinoma in Chinese Han.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6053-6053
Author(s):  
Hanyi Zhang ◽  
Shun Lu ◽  
Jinyi Lang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Single Nucleotide Polymorphisms ◽  
Association Studies ◽  
Sample Size Calculation ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Jnk Signaling ◽  
Increased Risk

6053 Background: Nasopharyngeal Carcinoma(NPC) is an Epstein-Barr virus(EBV) associated malignancy with remarkable ethnic and geographical distribution. The EBV oncoprotein latent membrane protein 1 (LMP1) is the primary oncogene of EBV infection through the its signaling cascade and its connections to other pathways including NF-κB, TGF-β and JNK signaling, which plays an important role in the pathogenesis of NPC. In GWASs(Genome-wide association studies) associations these pathways were also identified. Single nucleotide polymorphisms (SNPs) in the regulatory regions may regulate the expression of genes in these pathways, or affect the function of the coded protein. Methods: Altogether 149 SNPs were covered by the 15 SNPs in the TRAF2, TRAF3, NFKBIA, MAP2K4, and CHUK genes were genotyped in a hospital-based case-control study of 350 NPC cases and 587 healthy controls from the Chinese Han. The observed genotype frequencies in the controls were tested for Hardy–Weinberg equilibrium (HWE) using the chi-square test. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between genotypes and NPC risk and tumor characteristics were calculated by logistic regression, and they were adjusted for multiple testing using the SNP spectral deposition (SNPSpD) approach for multilocus analyses. Results: We found one NFKBIA SNP was associated with NPC risk after adjustment for multiple comparisons. Minor allele carriers of the NFKBIA had an increased risk of NPC (P < 0.05). The analyses were adjusted for age and gender. For a polymorphism with a variant allele frequency between 10 %and 50%, the study had greater than 90% power to detect an OR of 1.50 at a significance level of 0.05 (PS—software for power and sample size calculation, http://biostat.mc.vanderbilt.edu/twiki/bin/view/Main/PowerSampleSize). The other genotyped SNPs were not associated with NPC risk. Conclusions: Our data suggests that genetic variation especially in the NFKBIA maybe a useful biomarker for NPC screening and further studies are warranted.

scholarly journals Analysis of Single Nucleotide Polymorphisms within ADAM12 and Risk of Knee Osteoarthritis in a Chinese Han Population

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Lin Wang ◽  
Lin Guo ◽  
Fengde Tian ◽  
Ruihu Hao ◽  
Tiejun Yang
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Population Based ◽  
Recessive Model ◽  
Chinese Han Population ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Han Population ◽  
Genotype Frequencies ◽  
Increased Risk

Objective. Osteoarthritis (OA) is a complex arthritic condition in which the genetic factor plays a major role. One of the candidate genes of is the ADAM12 gene, but no consistency has been reached till now. This study aims to investigate the potential role of four single nucleotide polymorphisms (SNPs) of the ADAM12 gene in susceptibility to knee OA and its progression in Chinese Han population.Methods. The rs1278279, rs3740199, rs1044122, and rs1871054 polymorphisms were genotyped and compared in a population based cohort consisting of 164 OA subjects and 200 age- and gender-matched controls.Results. The SNP rs1871054 was found with increased risk of OA susceptibility in comparing the genotype frequencies between the case and control groups no matter for which model of comparison (allele level, dominant model, recessive model, and extreme genotype model). Additionally, the SNP rs1871054 was found associated with increased OA severity according to the K/L grade.Conclusion. In summary, we have identified that the rs1871054 variant within the ADAM12 gene is a risk factor for increased osteoarthritis susceptibility and severity.

scholarly journals Meta-Analysis of Allergy Genome-Wide Association Studies

2020 ◽  
Author(s):  
Ronin Sharma
Keyword(s):  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Significance Level ◽  
Genome Wide ◽  
Linear Regressions

AbstractAllergies are complex conditions involving both environmental and genetic factors. The genetic basis underlying allergic disease is investigated through genetic association studies. Genome-wide association studies (GWAS) leverage sequenced data to identify genetic mutations, such as single-nucleotide polymorphisms (SNPs), associated with phenotypes of interest. Machine learning can be used to analyze large datasets and generate predictive models. In this study, several classification models were created to predict the significance level of SNPs associated with allergies. Summary statistics were obtained from the GWAS Catalog and combined from several studies. Biological features such as chromosomal location, base pair location, effect allele, and odds ratio were used to train the models. The models ranged from simple linear regressions to multi-layer neural networks. The final models reached accuracies of 80% and reflect the features that have the largest impact on a SNP’s association level.

scholarly journals Genetic risk factors associated with gestational diabetes in a multi-ethnic population

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261137
Author(s):  
Paula Benny ◽  
Hyeong Jun Ahn ◽  
Janet Burlingame ◽  
Men-Jean Lee ◽  
Corrie Miller ◽  
...  
Keyword(s):  
Gestational Diabetes ◽  
Association Studies ◽  
Pacific Islanders ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Multiethnic Cohort ◽  
Increased Risk

Aims Genome-wide association studies have shown an increased risk of type-2-diabetes (T2DM) in patients who carry single nucleotide polymorphisms in several genes. We investigated whether the same gene loci confer a risk for gestational diabetes mellitus (GDM) in women from Hawaii, and in particular, Pacific Islander and Filipino populations. Methods Blood was collected from 291 women with GDM and 734 matched non-diabetic controls (Pacific Islanders: 71 GDM, 197 non-diabetic controls; Filipinos: 162 GDM, 395 controls; Japanese: 58 GDM, 142 controls). Maternal DNA was used to genotype and show allele frequencies of 25 different SNPs mapped to 18 different loci. Results After adjusting for age, BMI, parity and gravidity by multivariable logistic regression, several SNPs showed significant associations with GDM and were ethnicity specific. In particular, SNPs rs1113132 (EXT2), rs1111875 (HHEX), rs2237892 (KCNQ1), rs2237895 (KCNQ1), rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM in Filipinos. For Japanese, SNPs rs4402960 (IGFBP2) and rs2237892 (KCNQ1) were significantly associated with GDM. For Pacific Islanders, SNPs rs10830963 (MTNR1B) and rs13266634 (SLC30A8) showed significant associations with GDM. Individually, none of the SNPs showed a consistent association with GDM across all three investigated ethnicities. Conclusion Several SNPs associated with T2DM are found to confer increased risk for GDM in a multiethnic cohort in Hawaii.

Association between ADAMTS7 TagSNPs and the risk of myocardialinfarction

2019 ◽  
Vol 95 (1127) ◽  
pp. 487-492
Author(s):  
Li-li Liang ◽  
Yu-lan Zhou ◽  
Jie Cheng ◽  
Yu-tong Xiao ◽  
Zi-bin Tang ◽  
...  
Keyword(s):  
Association Studies ◽  
Multivariate Logistic Regression Analysis ◽  
Underlying Mechanism ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
General Validity ◽  
Genome Wide ◽  
Increased Risk ◽  
Stratified Analysis

Purpose of the studyGenome-wide association studies have revealed an association of ADAMTS7 polymorphisms with the risk of cardiovascular diseases. Nonetheless, the role of ADAMTS7 polymorphisms on myocardial infarction (MI) risk remains poorly understood. Here, we aim to evaluate the effect of ADAMTS7 tag single nucleotide polymorphisms (SNPs) on individual susceptibility to MI.Study designGenotyping of the four tagSNPs (rs1994016, rs3825807, rs4380028 and rs7173743) was performed in 232 MI cases and 661 control subjects using PCR-ligase detection reaction (LDR) method. The association of these four tagSNPs with MI risk was performed with SPSS software.ResultsMultivariate logistic regression analysis showed that ADAMTS7 tagSNP rs3825807 exhibited a significant effect on MI risk. Compared with the TT homozygotes, the CT genotype (OR1.93, 95% CI1.30to 2.85, Pc=0.004) and the combined CC/CT genotypes (OR1.70, 95% CI1.16 to 2.50, Pc=0.028) were statistically significantly associated with the increased risk for MI. Further stratified analysis revealed a more significant association with MI risk among older subjects, hypertensives, non-diabetics and patients with hyperlipidaemia. Consistently, the haplotype rs1994016T–rs3825807C containing rs3825807 C allele exhibited increased MI risk (OR1.52, 95% CI1.10 to 2.10, p=0.010). However, we did not detect any association of the other three tagSNPs with MI risk.ConclusionsOur finding suggest that ADAMTS7 tagSNP rs3825807 contributes to MI susceptibility in the Chinese Han population. Further studies are necessary to confirm the general validity of our findings and to clarify the underlying mechanism for this association.

SYNJ2 Variant Rs9365723 is Associated with Colorectal Cancer Risk in Chinese Han Population

2016 ◽  
Vol 31 (2) ◽  
pp. 138-143 ◽  
Author(s):  
Qingguo Du ◽  
Xueyan Guo ◽  
Xiyang Zhang ◽  
Wenjing Zhou ◽  
Zhuo Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Genetic Model ◽  
Association Studies ◽  
Chinese Han Population ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Han Population ◽  
Increased Risk

Purpose Colorectal cancer (CRC) is the third most common cancer and fourth leading cause of cancer mortality, and twin studies have shown that approximately 35% of the variation in susceptibility to CRC involves inherited genetic differences. We sought to investigate potential genetic associations between some single nucleotide polymorphisms (SNPs) and the risk of CRC in the Chinese Han population. Methods We conducted a case-control study including 269 cases and 309 controls. Sixteen SNPs associated with CRC risk were selected from previous genome-wide association studies and genotyped using Sequenom MassARRAY technology. Odds ratios and 95% confidence intervals (CIs) were calculated by unconditional logistic regression adjusting for age and gender. Results Using the chi-squared test we found that rs9365723 was associated with CRC risk (p = 0.012). With genetic model analysis, the genotype A/G-G/G (OR = 1.50; 95% CI 1.02-2.21; p = 0.038) of rs9365723 showed an increased risk of CRC in the dominant model. Furthermore, we found that rs9365723 was associated with an increased risk only for colon cancer but not rectal cancer (p = 0.009 and p = 0.414, respectively). Conclusions Our results, combined with previous studies, suggest that rs9365723, located on SYNJ2, is associated with the risk of CRC in a Chinese population. Thus, SYNJ2 may play a role in the development of CRC, especially colon cancer.

scholarly journals Exploration of CYP21A2 and CYP17A1 polymorphisms and preeclampsia risk among Chinese Han population: a large-scale case-control study based on 5021 subjects

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Bo Hou ◽  
Xuewen Jia ◽  
Ziwen Deng ◽  
Xin Liu ◽  
Huitang Liu ◽  
...  
Keyword(s):  
Large Scale ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Single Nucleotide ◽  
Allelic Frequencies ◽  
Genome Wide ◽  
And Control ◽  
The Relationship

Abstract Background Several genome-wide association studies have identified single-nucleotide polymorphisms (SNPs), such as rs4409766, rs1004467, and rs3824755 in CYP17A1 and rs2021783 in CYP21A2, as new hypertension susceptibility genetic variants in the Chinese population. This study aimed to look into the relationship between preeclampsia (PE) and these SNPs in Chinese Han women. Methods Overall, 5021 unrelated pregnant women were recruited, including 2002 patients with PE and 3019 normal healthy controls. The real-time PCR (TaqMan) method was applied to genotype these four polymorphisms. Results A statistically obvious difference in the allelic frequencies was observed in CYP21A2 rs2021783 between cases and controls (χ2 = 7.201, Pc = 0.028 by allele), and the T allele was associated with the occurrence and development of PE (OR = 1.151, 95% CI 1.039–1.275). We also found a significant association between rs2021783 and the development of early-onset PE (Pc = 0.008 by genotype, Pc = 0.004 by allele). For rs1004467 and rs3824755, the distribution of allelic frequencies differed markedly between mild PE and control groups (χ2 = 6.843, Pc = 0.036; χ2 = 6.869, Pc = 0.036), and patients with the TT genotype of rs1004467 were less easy to develop mild PE than were those carrying the CT or CC genotype (χ2 = 7.002, Pc = 0.032, OR = 1.306, 95% CI 1.071–1.593). The GG genotype of rs3824755 appeared to a protective effect on the occurrence of mild PE (OR = 0.766, 95% CI 0.629–0.934). Conclusions CYP21A2 rs2021783 appears to be closely related to PE susceptibility, and CYP17A1 rs1004467 and rs3824755 seem to be closely associated with mild PE in Han women.

scholarly journals Genetic Predisposition and Salt Sensitivity in a Chinese Han Population: The EpiSS Study

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Kuo Liu ◽  
Bo Xi ◽  
Zheng Liu ◽  
Han Qi ◽  
Bin Liu ◽  
...  
Keyword(s):  
Association Studies ◽  
Joint Effect ◽  
Salt Sensitivity ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chinese Han ◽  
Salt Loading ◽  
Risk Variants ◽  
Increased Risk

Objectives. Genome-wide association studies and candidate gene studies have found many single nucleotide polymorphisms (SNPs) that affect salt sensitivity (SS). We constructed a polygenic risk score (PRS) to estimate the joint effect of these SNPs on SS. Methods. We recruited 762 Chinese participants into the study. An unweighted PRS was constructed using 42 known genetic risk variants associated with SS or salt sensitivity blood pressure. A modified Sullivan’s acute oral saline load and diuresis shrinkage test was used to detect salt sensitivity. Logistic regression was used to estimate the joint effect of the SNPs on SS both overall and after stratification by hypertension. Results. The mean age of the participants was 57.1 years, and most of them were female (77.4%). The prevalence of SS was 28.7%. Both the continuous PRS and PRS tertiles were significantly associated with the risk of SS and a BP increase of more than 5 mmHg during acute salt loading but were not associated with a BP decrease of more than 10 mmHg during the diuresis shrinkage process. In the normotensive group, participants with PRSs in the middle and top tertiles had a more than twofold increased risk of SS (OR = 2.18, 95% CI: 1.15–4.12, P=0.016, and OR = 2.28, 95% CI: 1.19–4.38, P=0.013, respectively) compared with participants with PRSs in the first tertile. In the normotensive group, participants with PRSs in the middle tertile (OR = 1.94, 95% CI: 1.01–3.71, P=0.046) and top tertile (OR = 2.30, 95% CI: 1.19–4.44, P=0.013) had an increased risk of a greater than 5 mmHg increase in BP during acute salt loading than those with PRSs in the first tertile. In the hypertension group, neither the continuous PRS nor PRS tertile was significantly associated with the risk of SS. Conclusion. The 42 investigated SNPs were jointly and significantly associated with SS, especially in the normotensive Chinese population. These findings may provide genetic evidence for identifying target populations that would benefit from salt restriction policies.

scholarly journals Genetics of complex traits: prediction of phenotype, identification of causal polymorphisms and genetic architecture

2016 ◽  
Vol 283 (1835) ◽  
pp. 20160569 ◽  
Author(s):  
M. E. Goddard ◽  
K. E. Kemper ◽  
I. M. MacLeod ◽  
A. J. Chamberlain ◽  
B. J. Hayes
Keyword(s):  
Complex Traits ◽  
Genetic Architecture ◽  
Quantitative Traits ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Crop Breeding ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Phenotype Identification

Complex or quantitative traits are important in medicine, agriculture and evolution, yet, until recently, few of the polymorphisms that cause variation in these traits were known. Genome-wide association studies (GWAS), based on the ability to assay thousands of single nucleotide polymorphisms (SNPs), have revolutionized our understanding of the genetics of complex traits. We advocate the analysis of GWAS data by a statistical method that fits all SNP effects simultaneously, assuming that these effects are drawn from a prior distribution. We illustrate how this method can be used to predict future phenotypes, to map and identify the causal mutations, and to study the genetic architecture of complex traits. The genetic architecture of complex traits is even more complex than previously thought: in almost every trait studied there are thousands of polymorphisms that explain genetic variation. Methods of predicting future phenotypes, collectively known as genomic selection or genomic prediction, have been widely adopted in livestock and crop breeding, leading to increased rates of genetic improvement.

scholarly journals Upregulation of c-MYC in cis through a Large Chromatin Loop Linked to a Cancer Risk-Associated Single-Nucleotide Polymorphism in Colorectal Cancer Cells

2010 ◽  
Vol 30 (6) ◽  
pp. 1411-1420 ◽  
Author(s):  
Jason B. Wright ◽  
Seth J. Brown ◽  
Michael D. Cole
Keyword(s):  
Cancer Risk ◽  
Cancer Cells ◽  
Association Studies ◽  
Beta Catenin ◽  
Genome Wide Association Studies ◽  
Chromatin Loop ◽  
Nucleotide Polymorphisms ◽  
Distal Enhancer ◽  
Enhancer Activity ◽  
Single Nucleotide

ABSTRACT Genome-wide association studies have mapped many single-nucleotide polymorphisms (SNPs) that are linked to cancer risk, but the mechanism by which most SNPs promote cancer remains undefined. The rs6983267 SNP at 8q24 has been associated with many cancers, yet the SNP falls 335 kb from the nearest gene, c-MYC. We show that the beta-catenin-TCF4 transcription factor complex binds preferentially to the cancer risk-associated rs6983267(G) allele in colon cancer cells. We also show that the rs6983267 SNP has enhancer-related histone marks and can form a 335-kb chromatin loop to interact with the c-MYC promoter. Finally, we show that the SNP has no effect on the efficiency of chromatin looping to the c-MYC promoter but that the cancer risk-associated SNP enhances the expression of the linked c-MYC allele. Thus, cancer risk is a direct consequence of elevated c-MYC expression from increased distal enhancer activity and not from reorganization/creation of the large chromatin loop. The findings of these studies support a mechanism for intergenic SNPs that can promote cancer through the regulation of distal genes by utilizing preexisting large chromatin loops.

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