scholarly journals Association between 20q12 rs13041247 polymorphism and risk of nonsyndromic cleft lip with or without cleft palate: a meta-analysis

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Liheng Huang ◽  
Xinglong Liang ◽  
Yangzhan Ou ◽  
Shijie Tang ◽  
Yunpu He
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Case Control Studies ◽  
Chromosomal Locus ◽  
Asian Ethnicity ◽  
Study Population

Abstract Background Previous genome-wide association studies have identified a link between the rs13041247 single nucleotide polymorphisms (SNPs) in the chromosome 20q12 locus and the development of the congenital malformation known as nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present meta-analysis was therefore designed to formally assess the relationship between rs13041247 and NSCL/P. Methods We searched Embase, Web of Science, PubMed, the China National Knowledge Internet (CNKI), and the China Wanfang database in order to identify relevant published through 25 June 2019. This allowed us to identify 13 studies incorporating 4914 patients and 5981 controls for whom rs13041247 genotyping had been conducted, with STATA 12.0 then being used to conduct a meta-analysis of these pooled results. The I2 statistic was used to compare heterogeneity among studies. Results In total this analysis incorporated 13 case-control studies. No association between the rs13041247 polymorphism and NSCL/P risk was detected in individuals of Asian ethnicity (C vs T: OR = 0.847, 95% CI = 0.702–1.021; CC vs TT: OR = 0.725, 95% CI = 0.494–1.063; CC vs CT: OR = 0.837, 95% CI = 0.657–1.067; CT + TT vs CC: OR = 1.265, 95% CI = 0.951–1.684; CC + CT vs TT: OR = 0.805, 95% CI = 0.630–1.029) or Caucasian ethnicity (C vs T: OR = 0.936, 95% CI = 0.786–1.114; CC vs TT: OR = 0.988, 95% CI = 0.674–1.446; CC vs CT: OR = 1.197, 95% CI = 0.816–1.757; CT + TT vs CC: OR = 0.918, 95% CI = 0.639–1.318; CC + CT vs TT: OR = 0.855, 95% CI = 0.677–1.081). However, an overall analysis of all participants in these studies revealed the rs13041247 C allele, the CT genotype, and the CC + CT model to be linked to a reduced NSCL/P risk (C vs T: OR = 0.897, 95% CI: 0.723–1.114, P = 0.048; CT vs TT: OR = 0.839, 95% CI: 0.734–0.959, P = 0.01; CC + CT vs TT: OR = 0.824, 95% CI: 0.701–0.968, P = 0.019). Conclusion These results suggest that the rs13041247 SNP located at the 20q12 chromosomal locus is associated with NSCL/P risk in an overall pooled study population, although this association was not significant in East Asian or Caucasian populations.

scholarly journals Comorbidities and Susceptibility to COVID-19: A Generalized Gene Set Data Mining Approach

2021 ◽  
Vol 10 (8) ◽  
pp. 1666
Author(s):  
Micaela F. Beckman ◽  
Farah Bahrani Mougeot ◽  
Jean-Luc C. Mougeot
Keyword(s):  
Protein Interactions ◽  
Association Studies ◽  
Meta Analysis ◽  
Holistic Approach ◽  
Gene Interaction ◽  
Snp Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Protein Protein Interactions ◽  
Data Mining Approach

The COVID-19 pandemic has led to over 2.26 million deaths for almost 104 million confirmed cases worldwide, as of 4 February 2021 (WHO). Risk factors include pre-existing conditions such as cancer, cardiovascular disease, diabetes, and obesity. Although several vaccines have been deployed, there are few alternative anti-viral treatments available in the case of reduced or non-existent vaccine protection. Adopting a long-term holistic approach to cope with the COVID-19 pandemic appears critical with the emergence of novel and more infectious SARS-CoV-2 variants. Our objective was to identify comorbidity-associated single nucleotide polymorphisms (SNPs), potentially conferring increased susceptibility to SARS-CoV-2 infection using a computational meta-analysis approach. SNP datasets were downloaded from a publicly available genome-wide association studies (GWAS) catalog for 141 of 258 candidate COVID-19 comorbidities. Gene-level SNP analysis was performed to identify significant pathways by using the program MAGMA. An SNP annotation program was used to analyze MAGMA-identified genes. Differential gene expression was determined for significant genes across 30 general tissue types using the Functional and Annotation Mapping of GWAS online tool GENE2FUNC. COVID-19 comorbidities (n = 22) from six disease categories were found to have significant associated pathways, validated by Q–Q plots (p < 0.05). Protein–protein interactions of significant (p < 0.05) differentially expressed genes were visualized with the STRING program. Gene interaction networks were found to be relevant to SARS and influenza pathogenesis. In conclusion, we were able to identify the pathways potentially affected by or affecting SARS-CoV-2 infection in underlying medical conditions likely to confer susceptibility and/or the severity of COVID-19. Our findings have implications in future COVID-19 experimental research and treatment development.

scholarly journals EGFR Polymorphism and Survival of NSCLC Patients Treated with TKIs: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Vladimir Jurisic ◽  
Vladimir Vukovic ◽  
Jasmina Obradovic ◽  
Lyudmila F. Gulyaeva ◽  
Nikolay E. Kushlinskii ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Association Studies ◽  
Meta Analysis ◽  
Growth Factor Receptor ◽  
Fixed Effect Model ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Ca Repeat ◽  
Meta Analyses ◽  
Nsclc Patients

Tyrosine kinase inhibitor- (TKI-) based therapy revolutionized the overall survival and the quality of life in non-small-cell lung cancer (NSCLC) patients that have epidermal growth factor receptor (EGFR) mutations. However, EGFR is a highly polymorphic and mutation-prone gene, with over 1200 single nucleotide polymorphisms (SNPs). Since the role of EFGR polymorphism on the treatment outcome is still a matter of debate, this research analyzed the available literature data, according to the PRISMA guidelines for meta-analyses. Research includes PubMed, Scopus, ISI Web of Science, and 14 of genome-wide association studies (GWAS) electronic databases in order to provide quantitative assessment of the association between ten investigated EGFR SNPs and the survival of NSCLC patients. The pooled HR and their 95% CI for OS and PFS for different EGFR polymorphisms using a random or fixed effect model based on the calculated heterogeneity between the studies was applied. The longest and the shortest median OSs were reported for the homozygous wild genotype and a variant allele carriers for rs712829 (-216G>T), respectively. Quantitative synthesis in our study shows that out of ten investigated EGFR SNPs (rs11543848, rs11568315, rs11977388, rs2075102, rs2227983, rs2293347, rs4947492, rs712829, rs712830, and rs7809028), only four, namely, rs712829 (-216G>T), rs11568315 (CA repeat), rs2293347 (D994D), and rs4947492, have been reported to affect the outcome of TKI-based NSCLC treatment. Of these, only -216G>T and variable CA repeat polymorphisms have been confirmed by meta-analysis of available data to significantly affect OS and PFS in gefitinib- or erlotinib-treated NSCLC patients.

scholarly journals TAGOOS: genome-wide supervised learning of non-coding loci associated to complex phenotypes

2019 ◽  
Vol 47 (14) ◽  
pp. e79-e79
Author(s):  
Aitor González ◽  
Marie Artufel ◽  
Pascal Rihet
Keyword(s):  
Cleft Lip ◽  
Association Studies ◽  
Area Under The Curve ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Functional Snps ◽  
Functional Regions ◽  
Complex Phenotypes ◽  
Genome Wide ◽  
Intergenic Regions

Abstract Genome-wide association studies (GWAS) associate single nucleotide polymorphisms (SNPs) to complex phenotypes. Most human SNPs fall in non-coding regions and are likely regulatory SNPs, but linkage disequilibrium (LD) blocks make it difficult to distinguish functional SNPs. Therefore, putative functional SNPs are usually annotated with molecular markers of gene regulatory regions and prioritized with dedicated prediction tools. We integrated associated SNPs, LD blocks and regulatory features into a supervised model called TAGOOS (TAG SNP bOOSting) and computed scores genome-wide. The TAGOOS scores enriched and prioritized unseen associated SNPs with an odds ratio of 4.3 and 3.5 and an area under the curve (AUC) of 0.65 and 0.6 for intronic and intergenic regions, respectively. The TAGOOS score was correlated with the maximal significance of associated SNPs and expression quantitative trait loci (eQTLs) and with the number of biological samples annotated for key regulatory features. Analysis of loci and regions associated to cleft lip and human adult height phenotypes recovered known functional loci and predicted new functional loci enriched in transcriptions factors related to the phenotypes. In conclusion, we trained a supervised model based on associated SNPs to prioritize putative functional regions. The TAGOOS scores, annotations and UCSC genome tracks are available here: https://tagoos.readthedocs.io.

scholarly journals Physical activity and risk of Alzheimer disease

Neurology ◽  
2020 ◽  
Vol 95 (13) ◽  
pp. e1897-e1905
Author(s):  
Sebastian E. Baumeister ◽  
André Karch ◽  
Martin Bahls ◽  
Alexander Teumer ◽  
Michael F. Leitzmann ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alzheimer Disease ◽  
Association Studies ◽  
Vigorous Physical Activity ◽  
Primary Study ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
Inverse Variance ◽  
Study Population

ObjectiveEvidence from observational studies for the effect of physical activity on the risk of Alzheimer disease (AD) is inconclusive. We performed a 2-sample mendelian randomization analysis to examine whether physical activity is protective for AD.MethodsSummary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 patients with AD and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at p < 5 × 10−8 to be associated with average accelerations and 8 SNPs associated at p < 5 × 10−7 with vigorous physical activity (fraction of accelerations >425 milligravities) served as instrumental variables.ResultsThere was no association between genetically predicted average accelerations with the risk of AD (inverse variance weighted odds ratio [OR] per SD increment: 1.03, 95% confidence interval 0.97–1.10, p = 0.332). Genetic liability for fraction of accelerations >425 milligravities was unrelated to AD risk.ConclusionThe present study does not support a causal association between physical activity and risk of AD.

scholarly journals High Level of Uromodulin Increases the Risk of Hypertension: A Mendelian Randomization Study

2021 ◽  
Vol 8 ◽  
Author(s):  
Ruilian You ◽  
Lanlan Chen ◽  
Lubin Xu ◽  
Dingding Zhang ◽  
Haitao Li ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Inverse Variance ◽  
The Uk ◽  
High Level

Background: The association of uromodulin and hypertension has been observed in clinical studies, but not proven by a causal relationship. We conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between uromodulin and blood pressure.Methods: We selected single nucleotide polymorphisms (SNPs) related to urinary uromodulin (uUMOD) and serum uromodulin (sUMOD) from a large Genome-Wide Association Studies (GWAS) meta-analysis study and research in PubMed. Six datasets based on the UK Biobank and the International Consortium for Blood Pressure (ICBP) served as outcomes with a large sample of hypertension (n = 46,188), systolic blood pressure (SBP, n = 1,194,020), and diastolic blood pressure (DBP, n = 1,194,020). The inverse variance weighted (IVW) method was performed in uUMOD MR analysis, while methods of IVW, MR-Egger, Weighted median, and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were utilized on sUMOD MR analysis.Results: MR analysis of IVM showed the odds ratio (OR) of the uUMOD to hypertension (“ukb-b-14057” and “ukb-b-14177”) is 1.04 (95% Confidence Interval (CI), 1.03-1.04, P &lt; 0.001); the effect sizes of the uUMOD to SBP are 1.10 (Standard error (SE) = 0.25, P = 8.92E-06) and 0.03 (SE = 0.01, P = 2.70E-04) in “ieu-b-38” and “ukb-b-20175”, respectively. The β coefficient of the uUMOD to DBP is 0.88 (SE = 0.19, P = 4.38E-06) in “ieu-b-39” and 0.05 (SE = 0.01, P = 2.13E-10) in “ukb-b-7992”. As for the sUMOD, the OR of hypertension (“ukb-b-14057” and “ukb-b-14177”) is 1.01 (95% CI 1.01–1.02, all P &lt; 0.001). The β coefficient of the SBP is 0.37 (SE = 0.07, P = 1.26E-07) in “ieu-b-38” and 0.01 (SE = 0.003, P = 1.04E-04) in “ukb-b-20175”. The sUMOD is causally associated with elevated DBP (“ieu-b-39”: β = 0.313, SE = 0.050, P = 3.43E-10; “ukb-b-7992”: β = 0.018, SE = 0.003, P = 8.41E-09).Conclusion: Our results indicated that high urinary and serum uromodulin levels are potentially detrimental in elevating blood pressure, and serve as a causal risk factor for hypertension.

scholarly journals Silencing of the tRNA Modification Enzyme Cdkal1 Effects Functional Insulin Synthesis in NIT-1 Cells: tRNALys3 Lacking ms2- (ms2t6A37) is Unable to Establish Sufficient Anticodon:Codon Interactions to Decode the Wobble Codon AAG

2021 ◽  
Vol 7 ◽  
Author(s):  
Amithi Narendran ◽  
Sweta Vangaveti ◽  
Srivathsan V. Ranganathan ◽  
Emily Eruysal ◽  
Miranda Craft ◽  
...  
Keyword(s):  
Cell Line ◽  
Association Studies ◽  
Significant Risk ◽  
Genome Wide Association Studies ◽  
Trna Modification ◽  
Nucleotide Polymorphisms ◽  
Insulin Production ◽  
Case Control Studies ◽  
Knock Out ◽  
Insulin Synthesis

Human Genome Wide Association Studies found a significant risk of Type 2 Diabetes Mellitus (T2DM) in single nucleotide polymorphisms in the cdkal1 gene. The cdkal1 gene is remote from the insulin gene and with the surprising function of a specific tRNA modification. Population studies and case control studies acquired evidences of the connection between Cdkal1 protein and insulin production over the years. To obtain biochemical proofs directly linking potential SNPs to their roles in insulin production and availability is challenging, but the development of Cdkal1 knock out mice and knock out cell lines made it possible to extend our knowledge towards therapeutic field of diabetic research. Supporting the evidences, here we show that knock down of the cdkal1 gene using small interfering and short hairpin RNA in the NIT-1 cell line, a β-cell line inducible for insulin resulted in reduced levels of cdkal1 and mature insulin mRNAs, increased the level of precursor insulin mRNA, decreased Cdkal1 and insulin proteins, and diminished modification of tRNALys3 from t6A37 to ms2t6A37, the specified function of Cdkal1. tRNALys3 lacking ms2- is incapable of establishing sufficient hydrogen bonding energy and hydrophobic stabilization to decode the wobble codon AAG.

scholarly journals Efficacy of Periconceptional High-Dose Folic Acid in Isolated Orofacial Cleft Prevention: A Systematic Review

2019 ◽  
Vol 52 (02) ◽  
pp. 153-159 ◽  
Author(s):  
Rajshree Jayarajan ◽  
Anantharajan Natarajan ◽  
Ravindranathan Nagamuttu
Keyword(s):  
Folic Acid ◽  
High Risk ◽  
Cleft Palate ◽  
Cleft Lip ◽  
Meta Analysis ◽  
Strong Association ◽  
Folic Acid Supplementation ◽  
Case Control ◽  
High Dose ◽  
Case Control Studies

Abstract Background The effectiveness of folic acid in prevention of neural tube defects has been well established. Periconceptional supplementation of folic acid in low doses has been shown to be effective in some studies on its efficacy in prevention of occurrence of clefts. There are few studies on high-dose folic acid for prevention of occurrence and recurrence of clefts in high risk cases and the overall consensus based on these is not available. Objectives The aim of this review is to assess whether high-dose folic acid supplementation during the periconceptional period reduces the risk of occurrence of nonsyndromic clefts and recurrence in high-risk cases. Search Methods Search was conducted in the various databases and trial registers. There were no restrictions in the search with regards to language, study setting, or date of publication. Results The search yielded four studies—one randomized control trial, two prospective control trials, and a case–control surveillance on screening 401 articles. The three case–control studies were specifically on recurrence of clefts in high risk cases. The heterogeneity of the studies prevented conduction of a meta-analysis. But results of the studies demonstrate a strong association between high-dose folic acid and isolated nonsyndromic cleft lip with or without cleft palate (CL±CP). But such an effect is weak with regards to isolated cleft palate (CP). Conclusions With the limited evidence available, our conclusion is that high-dose folic acid probably has a role in prevention of recurrence of isolated CL±CP in high-risk individuals, but not CP.

Maternal Common Cold or Fever During Pregnancy and the Risk of Orofacial Clefts in the Offspring: A Systematic Review and Meta-analysis

2021 ◽  
pp. 105566562110676
Author(s):  
Fang-ping Shi ◽  
Ying-ying Huang ◽  
Qiao-qun Dai ◽  
Yu-lu Chen ◽  
Hai-yin Jiang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Common Cold ◽  
Cleft Lip ◽  
Meta Analysis ◽  
Case Control Studies ◽  
Orofacial Clefts ◽  
Random Effects Models ◽  
Relative Risks ◽  
Increased Risk ◽  
The Common

The common cold and/or an associated fever during pregnancy have/has been suspected to harm the developing fetus. We sought possible correlations between a maternal common cold or fever during pregnancy and the risk of orofacial clefts in the offspring. We systematically searched PubMed and Embase using appropriate keywords, and we checked the reference lists of retrieved articles. We used random-effects models to estimate overall relative risks. Incidence of orofacial clefts. We included 13 case-control studies. Modest but statistically significant associations were found between a maternal common cold and cleft lip with or without a cleft palate (CL/CP) (odds ratio [OR] 2.17; 95% confidence interval [CI] 1.66–2.83) and a cleft palate only (CPO) (OR 3.08; 95% CI 1.5–6.34). Furthermore, maternal fever was also associated with an increased risk of CL/CP (OR 1.91, 95% CI 1.3–2.8) and CPO (OR 1.48, 95% CI 0.83–2.63) in the offspring. Further analyses of maternal influenza (alone) yielded similar results. Although evidence of heterogeneity should be carefully evaluated, our findings suggest that maternal common cold or fever during pregnancy may be associated with a greater risk of CL/CP or CPO in the offspring. Future cohort studies using valid assessments of maternal common cold exposure during pregnancy that consider the severity of fever are needed to clarify the contribution of maternal common cold or fever status to the risk of orofacial clefts in children.

Sign in / Sign up

Export Citation Format

Share Document