Association between PRDM16, MEF2D, TRPM8, LRP1 gene polymorphisms and migraine susceptibility in the She ethnic population in China

Background: The prevalence of migraines in the She population, a minority in China, is significantly higher than that in Han Chinese and other Asian populations. Two single nucleotide polymorphisms (SNPs) have been found to be associated with migraine susceptibility in the She population. Purpose: This study investigated four SNPs, identified in genome-wide association studies, within migraine-susceptible loci in Han Chinese for their association with migraine susceptibility in the She population. Methods: Two-hundred unrelated migraine patients and 200 healthy controls were recruited. The SNPs examined included rs2651899 (PRDM16 ), rs2274316 (MEF2D ), rs7577262 (TRPM8) and rs11172113 (LRP1). Genotyping of the SNPs was performed by allele-specific polymerase chain reaction and direct sequencing. Results: No significant differences between the participants with migraines and controls (participants without migraines) were demonstrated in genotypes, alleles and allele carriage frequencies for the four SNPs. A subgroup analysis found that migraine with aura had a lower frequency of C allele positivity in rs2651899 than in healthy controls (59.6% vs. 74.5%, respectively; P < 0.034). Univariate analyses indicated that no genotype of the four SNPs had a significant association with migraines. Males had a lower risk of migraines, and advanced age was a significant risk factor for migraines in females. Conclusion: The SNPs in four migraine susceptible loci in Han Chinese were not risk factors for migraines in a relatively small sample of the She population.

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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

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2020.584228 ◽

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.

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Cigarette smoking and schizophrenia: Mendelian randomisation study

The British Journal of Psychiatry ◽

10.1192/bjp.2020.116 ◽

2020 ◽

pp. 1-6

Author(s):

Jianhua Chen ◽

Ruirui Chen ◽

Siying Xiang ◽

Ningning Li ◽

Chengwen Gao ◽

...

Keyword(s):

Cigarette Smoking ◽

Association Studies ◽

Smoking Initiation ◽

Sensitivity Analyses ◽

Mendelian Randomisation ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Complex Behaviour ◽

Asian Populations ◽

Smoking Behaviours

Background The link between schizophrenia and cigarette smoking has been well established through observational studies. However, the cause–effect relationship remains unclear. Aims We conducted Mendelian randomisation analyses to assess any causal relationship between genetic variants related to four smoking-related traits and the risk of schizophrenia. Method We performed a two-sample Mendelian randomisation using summary statistics from genome-wide association studies (GWAS) of smoking-related traits and schizophrenia (7711 cases, 18 327 controls) in East Asian populations. Single nucleotide polymorphisms (SNPs) correlated with smoking behaviours (smoking initiation, smoking cessation, age at smoking initiation and quantity of smoking) were investigated in relation to schizophrenia using the inverse-variance weighted (IVW) method. Further sensitivity analyses, including Mendelian randomisation-Egger (MR-Egger), weighted median estimates and leave-one-out analysis, were used to test the consistency of the results. Results The associated SNPs for the four smoking behaviours were not significantly associated with schizophrenia status. Pleiotropy did not inappropriately affect the results. Conclusions Cigarette smoking is a complex behaviour in people with schizophrenia. Understanding factors underlying the observed association remains important; however, our findings do not support a causal role of smoking in influencing risk of schizophrenia.

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VRK2 gene expression in schizophrenia, bipolar disorder and healthy controls

The British Journal of Psychiatry ◽

10.1192/bjp.bp.115.161950 ◽

2016 ◽

Vol 209 (2) ◽

pp. 114-120 ◽

Cited By ~ 11

Author(s):

Martin Tesli ◽

Katrine Verena Wirgenes ◽

Timothy Hughes ◽

Francesco Bettella ◽

Lavinia Athanasiu ◽

...

Keyword(s):

Gene Expression ◽

Bipolar Disorder ◽

Association Studies ◽

Mrna Level ◽

Genome Wide Association Studies ◽

Mrna Levels ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Schizophrenia Spectrum Disorders ◽

Underlying Mechanisms

BackgroundCommon variants in the Vaccinia-related kinase 2 (VRK2) gene have been associated with schizophrenia, but the relevance of its encoded protein VRK2 in the disorder remains unclear.AimsTo identify potential differences in VRK2 gene expression levels between schizophrenia, bipolar disorder, psychosis not otherwise specified (PNOS) and healthy controls.MethodVRK2 mRNA level was measured in whole blood in 652 individuals (schizophrenia, n = 201; bipolar disorder, n = 167; PNOS, n = 61; healthy controls, n = 223), and compared across diagnostic categories and subcategories. Additionally, we analysed for association between 1566 VRK2 single nucleotide polymorphisms and mRNA levels.ResultsWe found lower VRK2 mRNA levels in schizophrenia compared with healthy controls (P<10–12), bipolar disorder (P<10–12) and PNOS (P = 0.0011), and lower levels in PNOS than in healthy controls (P = 0.0042) and bipolar disorder (P = 0.00026). Expression quantitative trait loci in close proximity to the transcription start site of the short isoforms of the VRK2 gene were identified.ConclusionsAltered VRK2 gene expression seems specific for schizophrenia and PNOS, which is in accordance with findings from genome-wide association studies. These results suggest that reduced VRK2 mRNA levels are involved in the underlying mechanisms in schizophrenia spectrum disorders.

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Comparison of the Performance of Two Commercial Genome-Wide Association Study Genotyping Platforms in Han Chinese Samples

G3 Genes|Genome|Genetics ◽

10.1534/g3.112.004069 ◽

2013 ◽

Vol 3 (1) ◽

pp. 23-29 ◽

Cited By ~ 16

Author(s):

Lei Jiang ◽

Dana Willner ◽

Patrick Danoy ◽

Huji Xu ◽

Matthew A Brown

Keyword(s):

Allele Frequency ◽

Minor Allele Frequency ◽

Genome Wide Association Study ◽

Association Studies ◽

Han Chinese ◽

Minor Allele ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genome Wide

Abstract Most genome-wide association studies to date have been performed in populations of European descent, but there is increasing interest in expanding these studies to other populations. The performance of genotyping chips in Asian populations is not well established. Therefore, we sought to test the performance of widely used fixed-marker, genome-wide association studies chips in the Han Chinese population. Non-HapMap Chinese samples (n = 396) were genotyped using the Illumina OmniExpress and Affymetrix 6.0 platforms, whereas a subset also were genotyped using the Immunochip. Genotyped markers from the Affymetrix 6.0 and Illumina OmniExpress were used for full genome imputation based on the HapMap 2 JPT+CHB (Japanese from Tokyo, Japan and Chinese from Beijing, China) reference panel. The concordance between markers genotypes for the three platforms was very high whether directly genotyped or genotyped and imputed single nucleotide polymorphisms (SNPs; >99.8% for directly genotyped and >99.5% for genotyped and imputed SNPs, respectively) were compared. The OmniExpress chip data enabled more SNPs to be imputed, particularly SNPs with minor allele frequency >5%. The OmniExpress chip achieved better coverage of HapMap SNPs than the Affymetrix 6.0 chip (73.6% vs. 65.9%, respectively, for minor allele frequency >5%). The Affymetrix 6.0 and Illumina OmniExpress chip have similar genotyping accuracy and provide similar accuracy of imputed SNPs. The OmniExpress chip however provides better coverage of Asian HapMap SNPs, although its coverage of HapMap SNPs is moderate.

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IL2RA Allele Increases Risk of Neuromyelitis Optica in Southern Han Chinese

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100015973 ◽

2013 ◽

Vol 40 (6) ◽

pp. 832-835 ◽

Cited By ~ 6

Author(s):

Yongqiang Dai ◽

Jin Li ◽

Xiaonan Zhong ◽

Yuge Wang ◽

Wei Qiu ◽

...

Keyword(s):

Neuromyelitis Optica ◽

Genetic Factors ◽

Inflammatory Diseases ◽

Association Studies ◽

Han Chinese ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Complex Interactions ◽

Genome Wide

Background:Neuromyelitis optica (NMO) and multiple sclerosis (MS) are chronic neuro-inflammatory diseases believed to arise from complex interactions between environmental and genetic factors. Recently, single nucleotide polymorphisms (SNPs) in interleukin (IL)-2 and -7 receptor alpha genes have been identified as novel susceptibility alleles for MS in genome-wide association studies. However, similar research on NMO is limited. We aimed to investigate the association of IL2RA SNPs rs2104286 and rs12722489 and IL7RA SNP rs6897932 with Southern Han Chinese NMO and MS patients.Methods:Frequencies of the three SNPs were examined in Southern Han Chinese mS cases (n=78), NMS cases (n=67) and controls (n=133) using sequencing-based typing.Results:The rs2104286G frequency in the IL2RA gene was significantly higher in NMO patients than in controls (puncorr=0.013, pcorr=0.026, OR:1.942, 95%CI:1.146-3.291).Conclusion:The rs2104286 G allele in IL2RA is present at higher frequencies in NMO patients than in healthy controls within a Southern Han Chinese population.

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GWAS-Top Polymorphisms Associated With Late-Onset Alzheimer Disease in Brazil: Pointing Out Possible New Culprits Among Non-Coding RNAs

Frontiers in Molecular Biosciences ◽

10.3389/fmolb.2021.632314 ◽

2021 ◽

Vol 8 ◽

Author(s):

Gabriela Canalli Kretzschmar ◽

Nina Moura Alencar ◽

Saritha Suellen Lopes da Silva ◽

Carla Daniela Sulzbach ◽

Caroline Grisbach Meissner ◽

...

Keyword(s):

Large Scale ◽

Late Onset ◽

Association Studies ◽

Brazilian Population ◽

Functional Explanation ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Bioinformatic Tools ◽

Asian Populations ◽

Functional Investigation

Several genome-wide association studies (GWAS) have been carried out with late-onset Alzheimer’s disease (LOAD), mainly in European and Asian populations. Different polymorphisms were associated, but several of them without a functional explanation. GWAS are fundamental for identifying loci associated with diseases, although they often do not point to causal polymorphisms. In this sense, functional investigations are a fundamental tool for discovering causality, although the failure of this validation does not necessarily indicate a non-causality. Furthermore, the allele frequency of associated genetic variants may vary widely between populations, requiring replication of these associations in other ethnicities. In this sense, our study sought to replicate in 150 AD patients and 114 elderly controls from the South Brazilian population 18 single-nucleotide polymorphisms (SNPs) associated with AD in European GWAS, with further functional investigation using bioinformatic tools for the associated SNPs. Of the 18 SNPs investigated, only four were associated in our population: rs769449 (APOE), rs10838725 (CELF1), rs6733839, and rs744373 (BIN1–CYP27C1). We identified 54 variants in linkage disequilibrium (LD) with the associated SNPs, most of which act as expression or splicing quantitative trait loci (eQTLs/sQTLs) in genes previously associated with AD or with a possible functional role in the disease, such as CELF1, MADD, MYBPC3, NR1H3, NUP160, SPI1, and TOMM40. Interestingly, eight of these variants are located within long non-coding RNA (lncRNA) genes that have not been previously investigated regarding AD. Some of these polymorphisms can result in changes in these lncRNAs’ secondary structures, leading to either loss or gain of microRNA (miRNA)-binding sites, deregulating downstream pathways. Our pioneering work not only replicated LOAD association with polymorphisms not yet associated in the Brazilian population but also identified six possible lncRNAs that may interfere in LOAD development. The results lead us to emphasize the importance of functional exploration of associations found in large-scale association studies in different populations to base personalized and inclusive medicine in the future.

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Association of the ZC3H11B, ZFHX1B and SNTB1 genes with myopia of different severities

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2019-314203 ◽

2019 ◽

Vol 104 (10) ◽

pp. 1472-1476 ◽

Cited By ~ 5

Author(s):

Shu Min Tang ◽

Fen Fen Li ◽

Shi Yao Lu ◽

Ka Wai Kam ◽

Pancy O S Tam ◽

...

Keyword(s):

High Myopia ◽

Association Studies ◽

Susceptibility Gene ◽

Significant Risk ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Chinese Populations ◽

Genome Wide ◽

Chinese Cohort

ObjectiveTo investigate the associations of single-nucleotide polymorphisms (SNPs) in the ZC3H11B, ZFHX1B, VIPR2, SNTB1 and MIPEP genes with severities of myopia in Chinese populations.MethodsBased on previous myopia genome-wide association studies, five SNPs (ZC3H11B rs4373767, ZFHX1B rs13382811, VIPR2 rs2730260, SNTB1 rs7839488 and MIPEP rs9318086) were selected for genotyping in a Chinese cohort of 2079 subjects: 252 extreme myopia, 277 high myopia, 393 moderate myopia, 366 mild myopia and 791 non-myopic controls. Genotyping was performed by TaqMan assays. Allelic frequencies of the SNPs were compared with myopia severities and ophthalmic biometric measurements.ResultsThe risk allele T of ZC3H11B SNP rs4373767 was significantly associated with high myopia (OR=1.39, p=0.007) and extreme myopia (OR=1.34, p=0.013) when compared with controls, whereas ZFHX1B rs13382811 (allele T, OR=1.33, p=0.018) and SNTB1 rs7839488 (allele G, OR=1.71, p=8.44E-05) were significantly associated with extreme myopia only. In contrast, there was no significant association of these SNPs with moderate or mild myopia. When compared with mild myopia, subjects carrying T allele of rs4373767 had a risk of progressing to high myopia (spherical equivalent ≤−6 dioptres) (OR=1.29, p=0.017). Similarly, the T allele of rs13382811 also imposed a significant risk to high myopia (OR=1.36, p=0.007). In quantitative traits analysis, SNPs rs4373767, rs13382811 and rs7839488 were correlated with axial length and refractive errors.ConclusionsWe confirmed ZC3H11B as a susceptibility gene for high and extreme myopia, and ZFHX1B and SNTB for extreme myopia in Chinese populations. Instead of myopia onset, these three genes were more likely to impose risks of progressing to high and extreme myopia.

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mGWAS identification of six novel single nucleotide polymorphism loci with strong correlation to gastric cancer

Cancer & Metabolism ◽

10.1186/s40170-021-00269-2 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Shuangfeng Yang ◽

Yuan-Liang Wang ◽

Yanping Lyu ◽

Yu Jiang ◽

Jianjun Xiang ◽

...

Keyword(s):

Gastric Cancer ◽

Association Studies ◽

Genetic Regulation ◽

Population Data ◽

Cell Receptor ◽

Genome Wide Association Studies ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genome Wide

Abstract Background Metabolite genome-wide association studies (mGWAS) are key for understanding the genetic regulation of metabolites in complex diseases including cancers. Although mGWAS has revealed hundreds of metabolomics quantitative trait loci (mQTLs) in the general population, data relating to gastric cancer (GC) are still incomplete. Methods We identified mQTLs associated with GC by analyzing genome-wide and metabolome-wide datasets generated from 233 GC patients and 233 healthy controls. Results Twenty-two metabolites were statistically different between GC cases and healthy controls, and all of them were associated with the risk of gastric cancer. mGWAS analyses further revealed that 9 single nucleotide polymorphisms (SNPs) were significantly associated with 3 metabolites. Of these 9 SNPs, 6 loci were never reported in the previous mGWAS studies. Surprisingly, 4 of 9 SNPs were significantly enriched in genes involved in the T cell receptor signaling pathway. Conclusions Our study unveiled several novel GC metabolite and genetic biomarkers, which may be implicated in the prevention and diagnosis of gastric cancer.

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Integrating RNA-Seq With GWAS Reveals a Novel SNP in Immune-Related HLA-DQB1 Gene Associated With Occupational Pulmonary Fibrosis Risk: A Multi-Stage Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.796932 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yan Zhou ◽

Yingyi Zhang ◽

Rui Zhao ◽

Zhounan Cheng ◽

Minzhu Tang ◽

...

Keyword(s):

Association Studies ◽

Additive Model ◽

Functional Expression ◽

Peripheral Blood Lymphocytes ◽

Fold Change ◽

Genome Wide Association Studies ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Rna Seq ◽

Multi Stage

ObjectiveTo evaluate the association between single-nucleotide polymorphisms (SNPs) in RNA-seq identified mRNAs and silicosis susceptibility.MethodsA comprehensive RNA-seq was performed to screen for differently expressed mRNAs in the peripheral blood lymphocytes of eight subjects exposed to silica dust (four silicosis cases and four healthy controls). Following this, the SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility, were screened through silicosis-related genome-wide association studies (GWAS) (155 silicosis cases and 141 healthy controls), whereas functional expression quantitative trait locus (eQTL)-SNPs were identified using the GTEx database. Finally, the association between functional eQTL-SNPs and silicosis susceptibility (194 silicosis cases and 235 healthy controls) was validated.ResultsA total of 70 differentially expressed mRNAs (fold change > 2 or fold change < 0.5, P < 0.05) was obtained using RNA-seq. Furthermore, 476 SNPs located on the shortlisted mRNAs, which may affect silicosis susceptibility (P < 0.05) were obtained using GWAS, whereas subsequent six functional eQTL-SNPs were identified. The mutant A allele of rs9273410 in HLA-DQB1 indicated a potential increase in silicosis susceptibility in the validation stage (additive model: odds ratio (OR)= 1.31, 95% confidence interval (CI) = 0.99–1.74, P = 0.061), whereas the combination of GWAS and the validation results indicated that the mutant A allele of rs9273410 was associated with increased silicosis susceptibility (additive model: OR = 1.35, 95% CI =1.09–1.68, P = 0.006).ConclusionThe mutant A allele of rs9273410 was associated with increased silicosis susceptibility by modulating the expression of HLA-DQB1.

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Trans-ethnic analysis reveals genetic and non-genetic associations with COVID-19 susceptibility and severity

10.1101/2020.09.04.20188318 ◽

2020 ◽

Cited By ~ 6

Author(s):

Janie F. Shelton ◽

Anjali J. Shastri ◽

Chelsea Ye ◽

Catherine H. Weldon ◽

Teresa Filshtein-Somnez ◽

...

Keyword(s):

Association Studies ◽

Economic Status ◽

Strong Association ◽

Significant Risk ◽

Significant Risk Factor ◽

Blood Type ◽

European Ancestry ◽

Genome Wide Association Studies ◽

Genetic Associations ◽

Wide Range

COVID-19 presents with a wide range of severity, from asymptomatic in some individuals to fatal in others. Based on a study of over one million 23andMe research participants, we report genetic and non-genetic associations with testing positive for COVID-19, respiratory symptoms, and hospitalization. Risk factors for hospitalization include advancing age, male sex, elevated body mass index, lower socio-economic status, non-European ancestry, and pre-existing cardio-metabolic and respiratory conditions. Using trans-ethnic genome-wide association studies, we identify a strong association between blood type and COVID-19 diagnosis, as well as a gene-rich locus on chr3p21.31 that is more strongly associated with outcome severity. While non-European ancestry was found to be a significant risk factor for hospitalization after adjusting for socio-demographics and pre-existing health conditions, we did not find evidence that these two primary genetic associations explain differences between populations in terms of risk for severe COVID-19 outcomes.

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