scholarly journals Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants

2016 ◽  
Vol 48 (11) ◽  
pp. 1418-1424 ◽  
Author(s):  
Ying Jin ◽  
Genevieve Andersen ◽  
Daniel Yorgov ◽  
Tracey M Ferrara ◽  
Songtao Ben ◽  
...  
Keyword(s):  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Autoimmune Vitiligo ◽  
Key Pathways

scholarly journals CCR1 regulatory variants linked to pulmonary macrophage recruitment in severe COVID-19

2021 ◽  
Author(s):  
Bernard Stikker ◽  
Grégoire Stik ◽  
Rudi Hendriks ◽  
Ralph Stadhouders
Keyword(s):  
Genetic Association ◽  
Chemokine Receptor ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Regulatory Regions ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Monocytes And Macrophages ◽  
Mechanistic Basis

AbstractGenome-wide association studies have identified 3p21.31 as the main risk locus for severe symptoms and hospitalization in COVID-19 patients. To elucidate the mechanistic basis of this genetic association, we performed a comprehensive epigenomic dissection of the 3p21.31 locus. Our analyses pinpoint activating variants in regulatory regions of the chemokine receptor-encoding CCR1 gene as potentially pathogenic by enhancing infiltration of monocytes and macrophages into the lungs of patients with severe COVID-19.

scholarly journals Genome-Wide Association Study of Meiotic Recombination Phenotypes

2016 ◽  
Vol 6 (12) ◽  
pp. 3995-4007 ◽  
Author(s):  
Ferdouse Begum ◽  
Reshmi Chowdhury ◽  
Vivian G Cheung ◽  
Stephanie L Sherman ◽  
Eleanor Feingold
Keyword(s):  
Meiotic Recombination ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Snp Array ◽  
Genome Wide Association ◽  
Chromosome 17 ◽  
Genome Wide Association Studies ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Meta Analyses

Abstract Meiotic recombination is an essential step in gametogenesis, and is one that also generates genetic diversity. Genome-wide association studies (GWAS) and molecular studies have identified genes that influence of human meiotic recombination. RNF212 is associated with total or average number of recombination events, and PRDM9 is associated with the locations of hotspots, or sequences where crossing over appears to cluster. In addition, a common inversion on chromosome 17 is strongly associated with recombination. Other genes have been identified by GWAS, but those results have not been replicated. In this study, using new datasets, we characterized additional recombination phenotypes to uncover novel candidates and further dissect the role of already known loci. We used three datasets totaling 1562 two-generation families, including 3108 parents with 4304 children. We estimated five different recombination phenotypes including two novel phenotypes (average recombination counts within recombination hotspots and outside of hotspots) using dense SNP array genotype data. We then performed gender-specific and combined-sex genome-wide association studies (GWAS) meta-analyses. We replicated associations for several previously reported recombination genes, including RNF212 and PRDM9. By looking specifically at recombination events outside of hotspots, we showed for the first time that PRDM9 has different effects in males and females. We identified several new candidate loci, particularly for recombination events outside of hotspots. These include regions near the genes SPINK6, EVC2, ARHGAP25, and DLGAP2. This study expands our understanding of human meiotic recombination by characterizing additional features that vary across individuals, and identifying regulatory variants influencing the numbers and locations of recombination events.

scholarly journals Genome-wide association studies and CRISPR/Cas9-mediated gene editing identify regulatory variants influencing eyebrow thickness in humans

PLoS Genetics ◽  
2018 ◽  
Vol 14 (9) ◽  
pp. e1007640 ◽  
Author(s):  
Sijie Wu ◽  
Manfei Zhang ◽  
Xinzhou Yang ◽  
Fuduan Peng ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Gene Editing ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Regulatory Variants ◽  
Genome Wide

scholarly journals Identification of deleterious and regulatory genomic variations in known asthma loci

2018 ◽  
Author(s):  
Matthew D. C. Neville ◽  
Jihoon Choi ◽  
Jonathan Lieberman ◽  
Qing Ling Duan
Keyword(s):  
Candidate Gene ◽  
Association Studies ◽  
Genome Wide Association ◽  
Whole Genome Sequencing Data ◽  
Sequence Variants ◽  
Genome Wide Association Studies ◽  
Sequencing Data ◽  
Regulatory Variants ◽  
Genome Wide ◽  
Regulatory Effects

AbstractBackgroundCandidate gene and genome-wide association studies have identified hundreds of asthma risk loci. The majority of associated variants, however, are not known to have any biological function and are believed to represent markers rather than true causative mutations. We hypothesized that many of these associated markers are in linkage disequilibrium (LD) with the elusive causative variants.MethodsWe compiled a comprehensive list of 447 asthma-associated variants previously reported in candidate gene and genome-wide association studies. Next, we identified all sequence variants located within the 304 unique genes using whole-genome sequencing data from the 1000 Genomes Project. Then, we calculated the LD between known asthma variants and the sequence variants within each gene. LD variants identified were then annotated to determine those that are potentially deleterious and/or functional (i.e. coding or regulatory effects on the encoded transcript or protein).ResultsWe identified 10,048 variants in LD (r2 > 0.6) with known asthma variants. Annotations of these LD variants revealed that several have potentially deleterious effects including frameshift, alternate splice site, stop-lost, and missense. Moreover, 24 of the LD variants have been reported to regulate gene expression as expression quantitative trait loci (eQTLs).ConclusionsThis study is proof of concept that many of the genetic loci previously associated with complex diseases such as asthma are not causative but represent markers of disease, which are in LD with the elusive causative variants. We hereby report a number of potentially deleterious and regulatory variants that are in LD with the reported asthma loci. These reported LD variants could account for the original association signals with asthma and represent the true causative mutations at these loci.

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