scholarly journals Dissecting the genetics of chronic mucus hypersecretion in smokers with and without COPD

2014 ◽  
Vol 45 (1) ◽  
pp. 60-75 ◽  
Author(s):  
Akkelies E. Dijkstra ◽  
H. Marike Boezen ◽  
Maarten van den Berge ◽  
Judith M. Vonk ◽  
Pieter S. Hiemstra ◽  
...  
Keyword(s):  
Genetic Model ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Chronic Obstructive ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Mucus Hypersecretion ◽  
Genome Wide

Smoking is a notorious risk factor for chronic mucus hypersecretion (CMH). CMH frequently occurs in chronic obstructive pulmonary disease (COPD). The question arises whether the same single-nucleotide polymorphisms (SNPs) are related to CMH in smokers with and without COPD.We performed two genome-wide association studies of CMH under an additive genetic model in male heavy smokers (≥20 pack-years) with COPD (n=849, 39.9% CMH) and without COPD (n=1348, 25.4% CMH), followed by replication and meta-analysis in comparable populations, and assessment of the functional relevance of significantly associated SNPs.Genome-wide association analysis of CMH in COPD and non-COPD subjects yielded no genome-wide significance after replication. In COPD, our top SNP (rs10461985, p=5.43×10−5) was located in the GDNF-AS1 gene that is functionally associated with the GDNF gene. Expression of GDNF in bronchial biopsies of COPD patients was significantly associated with CMH (p=0.007). In non-COPD subjects, four SNPs had a p-value <10−5 in the meta-analysis, including a SNP (rs4863687) in the MAML3 gene, the T-allele showing modest association with CMH (p=7.57×10−6, OR 1.48) and with significantly increased MAML3 expression in lung tissue (p=2.59×10−12).Our data suggest the potential for differential genetic backgrounds of CMH in individuals with and without COPD.

scholarly journals A meta-analysis of the genome-wide association studies on two genetically correlated phenotypes (self-reported headache and self-reported migraine) identifies four new risk loci for headaches (N=397,385)

2021 ◽  
Author(s):  
Weihua Meng ◽  
Parminder Reel ◽  
Charvi Nangia ◽  
Aravind Rajendrakumar ◽  
Harry Hebert ◽  
...  
Keyword(s):  
Association Studies ◽  
Meta Analysis ◽  
The Self ◽  
Genome Wide Association ◽  
P Value ◽  
Clinical Settings ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Genetic Mechanisms ◽  
The Uk

Headache is one of the commonest complaints that doctors need to address in clinical settings. The genetic mechanisms of different types of headache are not well understood. In this study, we performed a meta-analysis of genome-wide association studies (GWAS) on the self-reported headache phenotype from the UK Biobank cohort and the self-reported migraine phenotype from the 23andMe resource using the metaUSAT for genetically correlated phenotypes (N=397,385). We identified 38 loci for headaches, of which 34 loci have been reported before and 4 loci were newly identified. The LRP1-STAT6-SDR9C7 region in chromosome 12 was the most significantly associated locus with a leading P value of 1.24 x 10-62 of rs11172113. The ONECUT2 gene locus in chromosome 18 was the strongest signal among the 4 new loci with a P value of 1.29 x 10-9 of rs673939. Our study demonstrated that the genetically correlated phenotypes of self-reported headache and self-reported migraine can be meta-analysed together in theory and in practice to boost study power to identify more new variants for headaches. This study has paved way for a large GWAS meta-analysis study involving cohorts of different, though genetically correlated headache phenotypes.

scholarly journals The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies

Blood ◽  
2012 ◽  
Vol 119 (10) ◽  
pp. 2392-2400 ◽  
Author(s):  
Jessica Dennis ◽  
Candice Y. Johnson ◽  
Adeniyi Samuel Adediran ◽  
Mariza de Andrade ◽  
John A. Heit ◽  
...  
Keyword(s):  
Protein C ◽  
Genetic Model ◽  
Thrombus Formation ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Endothelial Protein C Receptor ◽  
Genome Wide ◽  
Study Results

Abstract The endothelial protein C receptor (EPCR) limits thrombus formation by enhancing activation of the protein C anticoagulant pathway, and therefore may play a role in the etiology of thrombotic disorders. The rs867186 single-nucleotide polymorphism in the PROCR gene (g.6936A > G, c.4600A > G), resulting in a serine-to-glycine substitution at codon 219, has been associated with reduced activation of the protein C pathway, although its association with thrombosis risk remains unclear. The present study is a highly comprehensive systematic review and meta-analysis, including unpublished genome-wide association study results, conducted to evaluate the evidence for an association between rs867186 and 2 common thrombotic outcomes, venous thromboembolism (VTE) and myocardial infarction (MI), which are hypothesized to share some etiologic pathways. MEDLINE, EMBASE, and HuGE Navigator were searched through July 2011 to identify relevant epidemiologic studies, and data were summarized using random-effects meta-analysis. Twelve candidate genes and 13 genome-wide association studies were analyzed (11 VTE and 14 MI, including 37 415 cases and 84 406 noncases). Under the additive genetic model, the odds of VTE increased by a factor of 1.22 (95% confidence interval, 1.11-1.33, P < .001) for every additional copy of the G allele. No evidence for association with MI was observed.

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 A trans-ancestral meta-analysis of genome-wide association studies reveals loci associated with childhood obesity

2019 ◽  
Vol 28 (19) ◽  
pp. 3327-3338 ◽  
Author(s):  
Jonathan P Bradfield ◽  
Suzanne Vogelezang ◽  
Janine F Felix ◽  
Alessandra Chesi ◽  
Øyvind Helgeland ◽  
...  
Keyword(s):  
Childhood Obesity ◽  
Late Onset ◽  
Association Studies ◽  
Meta Analysis ◽  
Causal Variant ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
South American ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

Abstract Although hundreds of genome-wide association studies-implicated loci have been reported for adult obesity-related traits, less is known about the genetics specific for early-onset obesity and with only a few studies conducted in non-European populations to date. Searching for additional genetic variants associated with childhood obesity, we performed a trans-ancestral meta-analysis of 30 studies consisting of up to 13 005 cases (≥95th percentile of body mass index (BMI) achieved 2–18 years old) and 15 599 controls (consistently &lt;50th percentile of BMI) of European, African, North/South American and East Asian ancestry. Suggestive loci were taken forward for replication in a sample of 1888 cases and 4689 controls from seven cohorts of European and North/South American ancestry. In addition to observing 18 previously implicated BMI or obesity loci, for both early and late onset, we uncovered one completely novel locus in this trans-ancestral analysis (nearest gene, METTL15). The variant was nominally associated with only the European subgroup analysis but had a consistent direction of effect in other ethnicities. We then utilized trans-ancestral Bayesian analysis to narrow down the location of the probable causal variant at each genome-wide significant signal. Of all the fine-mapped loci, we were able to narrow down the causative variant at four known loci to fewer than 10 single nucleotide polymorphisms (SNPs) (FAIM2, GNPDA2, MC4R and SEC16B loci). In conclusion, an ethnically diverse setting has enabled us to both identify an additional pediatric obesity locus and further fine-map existing loci.

scholarly journals RTN4 AND FBXL17 GENES ARE ASSOCIATED WITH CORONARY HEART DISEASE IN GENOME-WIDE ASSOCIATION ANALYSIS OF LITHUANIAN FAMILIES

2013 ◽  
Vol 16 (2) ◽  
pp. 17-22 ◽  
Author(s):  
I. Domarkienė ◽  
A. Pranculis ◽  
Š. Germanas ◽  
A. Jakaitienė ◽  
D. Vitkus ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Genetic Factors ◽  
Association Studies ◽  
Genome Wide Association ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Chd Risk ◽  
Genome Wide

ABSTRACT Coronary heart disease (CHD) is a complex and heterogeneous cardiovascular disease. There are many genome-wide association studies (GWAS) performed worldwide to extract the causative genetic factors. Moreover, each population may have some exceptional genetic characteristic. Thus, the background of our study is from the previous Lithuanian studies (the LiVicordia Project), which demonstrated the differences of the atherosclerosis process between Lithuanian and Swedish male individuals. In this study we performed GWAS of 32 families of Lithuanian origin in search of significant candidate genetic markers [single nucleotide polymorphisms (SNPs)] of CHD in this population. After careful clinical and biochemical phenotype evaluation, the ~770K SNPs genotyping (Illumina HumanOmniExpress- 12 v1.0 array) and familial GWAS analyses were performed. Twelve SNPs were found to be significantly associated with the CHD phenotype (p value <0.0001; the power >0.65). The odds ratio (OR) values were calculated. Two SNPs (rs17046570 in the RTN4 gene and rs11743737 in the FBXL17 gene) stood out and may prove to be important genetic factors for CHD risk. Our results correspond with the findings in other studies, and these two SNPs may be the susceptibility loci for CHD

scholarly journals Metanalysis of genome-wide association studies for panic disorder suggest pathways and mechanisms of pathogenesis

2018 ◽  
Author(s):  
Rhayra Xavier do Carmo Silva ◽  
Sueslene Prado Rocha ◽  
Dainara Pereira dos Santos Souza ◽  
Monica Gomes Lima-Maximino ◽  
Caio Maximino
Keyword(s):  
Panic Disorder ◽  
Inflammatory Responses ◽  
Drug Repositioning ◽  
Association Studies ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Mouse Strains ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

AbstractPanic disorder (PD) is characterized by abrupt surges of intense fear and distress. There is evidence for a genetic component in this disorder. We ran a meta-analysis of genome-wide association studies of patients with PD, and found 25 single-nucleotide polymorphisms that were associated with the disorder. Causal gene prediction based on these polymorphisms uncovered 20 hits. Exploratory analyses suggested that these genes formed interactor networks, which was enriched in signaling pathways associated with immune and inflammatory responses, as well as growth factors and other developmental mediators. A subset of genes is enriched in limbic regions of the human brain and in microglia and myelinating oligodendrocytes of mice. While these genes were not associated with relevant neurobehavioral phenotypes in mutant mice, expression levels of several causal genes in the amygdala, prefrontal cortex, hippocampus, hypothalamus, and adrenal gland of recombinant mouse strains was associated with endophenotypes of fear conditioning. Drug repositioning prediction was unsuccessful, but this does not discard these genes and pathways as targets for investigational drugs. In general,ASB3,EIF2S2, RASGRF2, andTRMT2B(and its coded proteins) emerged as interesting targets for mechanistic research on PD. These exploratory findings point towards hypotheses of pathogenesis and neuropharmacology that need to be further investigated.

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