scholarly journals Concordance of genetic risk across migraine subgroups: Impact on current and future genetic association studies

Cephalalgia ◽  
2014 ◽  
Vol 35 (6) ◽  
pp. 489-499 ◽  
Author(s):  
Dale R Nyholt ◽  
Verneri Anttila ◽  
Bendik S Winsvold ◽  
Tobias Kurth ◽  
Hreinn Stefansson ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Association Studies ◽  
Meta Analysis ◽  
Genetic Association Studies ◽  
Population Based ◽  
Significant Heterogeneity ◽  
Single Nucleotide ◽  
Disease Spectrum ◽  
Genome Wide ◽  
Genetic Overlap

Background There has been intensive debate whether migraine with aura (MA) and migraine without aura (MO) should be considered distinct subtypes or part of the same disease spectrum. There is also discussion to what extent migraine cases collected in specialised headache clinics differ from cases from population cohorts, and how female cases differ from male cases with respect to their migraine. To assess the genetic overlap between these migraine subgroups, we examined genome-wide association (GWA) results from analysis of 23,285 migraine cases and 95,425 population-matched controls. Methods Detailed heterogeneity analysis of single-nucleotide polymorphism (SNP) effects (odds ratios) between migraine subgroups was performed for the 12 independent SNP loci significantly associated ( p < 5 × 10−8; thus surpassing the threshold for genome-wide significance) with migraine susceptibility. Overall genetic overlap was assessed using SNP effect concordance analysis (SECA) at over 23,000 independent SNPs. Results Significant heterogeneity of SNP effects ( phet < 1.4 × 10−3) was observed between the MA and MO subgroups (for SNP rs9349379), and between the clinic- and population-based subgroups (for SNPs rs10915437, rs6790925 and rs6478241). However, for all 12 SNPs the risk-increasing allele was the same, and SECA found the majority of genome-wide SNP effects to be in the same direction across the subgroups. Conclusions Any differences in common genetic risk across these subgroups are outweighed by the similarities. Meta-analysis of additional migraine GWA datasets, regardless of their major subgroup composition, will identify new susceptibility loci for migraine.

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 Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population

Human Cell ◽  
2021 ◽  
Vol 34 (2) ◽  
pp. 293-299
Author(s):  
Makoto Kawaguchi ◽  
Akiyoshi Nakayama ◽  
Yuka Aoyagi ◽  
Takahiro Nakamura ◽  
Seiko Shimizu ◽  
...  
Keyword(s):  
Japanese Population ◽  
Association Studies ◽  
Meta Analysis ◽  
Elevated Serum ◽  
Common Type ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphism ◽  
Single Nucleotide ◽  
Replication Studies ◽  
Genome Wide

AbstractGout is a common type of acute arthritis that results from elevated serum uric acid (SUA) levels. Recent genome-wide association studies (GWASs) have revealed several novel single nucleotide polymorphism (SNPs) associated with SUA levels. Of these, rs10821905 of A1CF and rs1178977 of BAZ1B showed the greatest and the second greatest significant effect size for increasing SUA level in the Japanese population, but their association with gout is not clear. We examined their association with gout using 1411 clinically-defined Japanese gout patients and 1285 controls, and meta-analyzed our previous gout GWAS data to investigate any association with gout. Replication studies revealed both SNPs to be significantly associated with gout (P = 0.0366, odds ratio [OR] with 95% confidence interval [CI]: 1.30 [1.02–1.68] for rs10821905 of A1CF, P = 6.49 × 10–3, OR with 95% CI: 1.29 [1.07–1.55] for rs1178977 of BAZ1B). Meta-analysis also revealed a significant association with gout in both SNPs (Pmeta = 3.16 × 10–4, OR with 95% CI: 1.39 [1.17–1.66] for rs10821905 of A1CF, Pmeta = 7.28 × 10–5, OR with 95% CI 1.32 [1.15–1.51] for rs1178977 of BAZ1B). This study shows the first known association between SNPs of A1CF, BAZ1B and clinically-defined gout cases in Japanese. Our results also suggest a shared physiological/pathophysiological background between several populations, including Japanese, for both SUA increase and gout susceptibility. Our findings will not only assist the elucidation of the pathophysiology of gout and hyperuricemia, but also suggest new molecular targets.

scholarly journals Variation rs9929218 and Risk of the Colorectal Cancer and Adenomas: A Meta-analysis

2020 ◽  
Author(s):  
Huiyan Wang ◽  
Dongying Gu ◽  
Miao Yu ◽  
Yanjun Hu ◽  
Zhe Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Colorectal ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Accurate Approximation ◽  
Single Nucleotide ◽  
Genome Wide ◽  
Different Populations

Abstract Backgrounds: Genome-wide association studies (GWAS) have identified multiple common CRC-related (colorectal cancer) SNPs (single nucleotide polymorphisms) including the Cadherin 1(CDH1) rs9929218 may act by increasing the risk of colorectal cancer, colorectal adenoma, or both. These studies, however, reported inconsistent associations. Methods: To derive a more accurate approximation of the connection, we carried out a meta-analysis of 12 published pieces of research including 11,590 controls and 8,192 cases. We used odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the associations' strength.Results: Meta-analysis implied considerable association between CRC and rs9929218 (OR = 1.21, 95%CI 1.04-1.42 for GG versus AA; OR = 1.22, 95%CI 1.05-1.42 for GG/AG versus AA).In the subgroup analyses, significantly increased risks were found among Europeans.Conclusions: In summary, our meta-analysis studies in different populations confirmed that SNP rs9929218 is significantly associated with CRC risk and that this variant may have a greater impact on Europeans.

scholarly journals Association of Immune and Inflammatory Gene Polymorphism With the Risk of IgA Nephropathy: A Systematic Review and Meta-Analysis of 45 Studies

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaonan Ding ◽  
Yan Mei ◽  
Zhi Mao ◽  
Lingling Long ◽  
Qiuxia Han ◽  
...  
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Iga Nephropathy ◽  
Association Studies ◽  
Meta Analysis ◽  
Random Effect ◽  
Genetic Association Studies ◽  
Nucleotide Polymorphisms ◽  
Odds Ratios ◽  
Single Nucleotide ◽  
Pubmed Database

IgA nephropathy is the most prevalent primary glomerulonephritis worldwide, with identical immunopathological characteristics caused by multiple etiologies as well as influenced by geographical and ethnical factors. To elucidate the role of immunologic and inflammatory mechanisms in the susceptibility to IgA nephropathy, we explored single nucleotide polymorphisms of related molecules in the immune pathways. We searched the PubMed database for studies that involved all gene variants of molecules in the 20 immunologic and inflammatory pathways selected from the Kyoto Encyclopedia of Genes and Genomes database. The odds ratios with their corresponding 95% confidence intervals in six genetic models (allele model, dominant model, homozygote model, heterozygote model, overdominant model, and recessive model) were summarized using fixed or random effect models. Subgroup analysis was conducted based on different ethnicities with generalized odds ratios. Heterogeneity was evaluated using the Q and I2 tests. Begg’s funnel plot and Egger’s linear regression test were used to evaluating possible publication bias among the included studies, and sensitivity analysis was used to test the stability of the overall results. A total of 45 studies met our selection criteria and eight related genetic association studies were retrieved, including 320 single-nucleotide polymorphisms from 20 candidate pathways, ranging from 2000 to 2021. A total of 28,994 healthy people versus 20,600 IgA nephropathy patients were enrolled. Upon meta-analyzed results that TGFB1 (rs1800469, rs1982073, rs1800471), IL-1B (rs1143627), IL-18 (rs1946518), and TLR1 (rs5743557) showed effect with or without ethnicity difference. And 10 variants presented stable and robust related to IgA nephropathy. This research showed that genetic variants are related to the immunologic and inflammatory effects of IgA nephropathy pathogenesis. The meta-analysis results supported the previous researches, and may help deepen the understanding of pathogenesis and explore new targets for IgA nephropathy-specific immunotherapy.

scholarly journals Association of GAK rs1564282 With Susceptibility to Parkinson’s Disease in Chinese Populations

2021 ◽  
Vol 12 ◽  
Author(s):  
He Li ◽  
Chen Zhang ◽  
Yong Ji
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Odds Ratio ◽  
Association Studies ◽  
Meta Analysis ◽  
Significant Heterogeneity ◽  
Genome Wide Association Studies ◽  
Chinese Populations ◽  
Genome Wide ◽  
Significant Publication Bias

The susceptibility of the GAK rs1564282 variant in Parkinson’s disease (PD) in Europeans was identified using a series of published genome-wide association studies. Recently, some studies focused on the association between rs1564282 and PD risk in Chinese populations but with inconsistent results. Thus, we conducted an updated meta-analysis with a total of 7,881 samples (4,055 PD cases and 3,826 controls) from eligible studies. After excluding significant heterogeneity, we showed that the rs1564282 variant was significantly associated with PD in Chinese populations (p = 1.00E-04, odds ratio = 1.28 and 95% confidence interval = 1.16–1.42). The sensitivity analysis showed that the association between rs1564282 and PD was not greatly influenced, and there was no significant publication bias among the included studies. Consequently, this meta-analysis indicates that the GAK rs1564282 variant is significantly associated with susceptibility to PD in Chinese populations.

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