scholarly journals Identification of Susceptibility Genes of Adult Asthma in French Canadian Women

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Jean-Christophe Bérubé ◽  
Nathalie Gaudreault ◽  
Emilie Lavoie-Charland ◽  
Laura Sbarra ◽  
Cyndi Henry ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Functional Characterization ◽  
Susceptibility Genes ◽  
Adult Women ◽  
Eqtl Mapping ◽  
Nucleotide Polymorphisms ◽  
French Canadian ◽  
Individual Genotyping ◽  
Functional Locus ◽  
Asthma Patients

Susceptibility genes of asthma may be more successfully identified by studying subgroups of phenotypically similar asthma patients. This study aims to identify single nucleotide polymorphisms (SNPs) associated with asthma in French Canadian adult women. A pooling-based genome-wide association study was performed in 240 allergic asthmatic and 120 allergic nonasthmatic women. The top associated SNPs were selected for individual genotyping in an extended cohort of 349 asthmatic and 261 nonasthmatic women. The functional impact of asthma-associated SNPs was investigated in a lung expression quantitative trait loci (eQTL) mapping study (n=1035). Twenty-one of the 38 SNPs tested by individual genotyping showedPvalues lower than 0.05 for association with asthma.Cis-eQTL analyses supported the functional contribution of rs17801353 associated withC3AR1(P=7.90E-10). The asthma risk allele for rs17801353 is associated with higher mRNA expression levels ofC3AR1in lung tissue.In silicofunctional characterization of the asthma-associated SNPs also supported the contribution ofC3AR1and additional genes includingSYNE1,LINGO2, andIFNG-AS1. This pooling-based GWAS in French Canadian adult women followed by lung eQTL mapping suggestedC3AR1as a functional locus associated with asthma. Additional susceptibility genes were suggested in this homogenous subgroup of asthma patients.

Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

2011 ◽  
Vol 70 (10) ◽  
pp. 1793-1797 ◽  
Author(s):  
Patrick Danoy ◽  
Meng Wei ◽  
Hadler Johanna ◽  
Lei Jiang ◽  
Dongyi He ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Association Study ◽  
Chinese Population ◽  
Genome Wide Association Study ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Two Phase ◽  
Han Chinese Population

BackgroundThe genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations.ObjectiveTo investigate these associations in the Han Chinese population.MethodsHaplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2=0.8) across 19 distinct RA genomic regions. A two phase case–control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied.ResultsRobust association was detected for MMEL1 and CTLA4, and modest association was identified for another six loci: PADI4, STAT4, PRDM1, CDK6, TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10−5 unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4, significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10−5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed.ConclusionThis study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

scholarly journals Functional annotation of melanoma risk loci identifies novel susceptibility genes

2019 ◽  
Vol 41 (4) ◽  
pp. 452-457 ◽  
Author(s):  
Shenying Fang ◽  
Jiachun Lu ◽  
Xinke Zhou ◽  
Yuling Wang ◽  
Merrick I Ross ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Functional Annotation ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Susceptibility Genes ◽  
Chromatin Interaction ◽  
Cytokine Signaling ◽  
Nucleotide Polymorphisms ◽  
Melanoma Risk ◽  
Functional Variants

Abstract Genome-wide association study (GWAS)-identified single-nucleotide polymorphisms (SNPs) are tag SNPs located in both transcribed and non-coding regulatory DNA regions, rather than representing causal or functional variants for disease. To identify functional variants or genes for melanoma susceptibility, we used functional mapping and annotation (FUMA) to perform functional annotation of the summary statistics of 2541 significant melanoma risk SNPs (P &lt; 5 × 10−8) identified by GWAS. The original GWAS melanoma study included 15 990 cases and 26 409 controls, representing the largest international meta-analysis of melanoma susceptibility. We prioritized 330 unique genes, including those in immune cytokine signaling pathways, from 19 loci through positional, expression quantitative trait locus, and chromatin interaction mapping. In comparison, only 38 melanoma-related genes were identified in the original meta-analysis. In addition to the well-known melanoma susceptibility genes confirmed in the meta-analysis (MC1R, CDKN2A, TERT, OCA2 and ARNT/SETDB1), we also identified additional novel genes using FUMA to map SNPs to genes. Through chromatin interaction mapping, we prioritized IFNA7, IFNA10, IFNA16, IFNA17, IFNA14, IFNA6, IFNA21, IFNA4, IFNE and IFNA5; these 10 most significant genes are all involved in immune system and cytokine signaling pathways. In the gene analysis, we identified 72 genes with a P &lt; 2.5 × 10−6. The genes associated with melanoma risk were DEF8 (P = 1.09 × 10−57), DBNDD1 (P = 2.19 × 10−42), SPATA33 (P = 3.54 × 10−38) and MC1R (P = 1.04 × 10−36). In summary, this study identifies novel putative melanoma susceptibility genes and provides a guide for further experimental validation of functional variants and disease-related genes.

Genome-wide association study identifies novel susceptibility loci for migraine in Han Chinese resided in Taiwan

Cephalalgia ◽  
2017 ◽  
Vol 38 (3) ◽  
pp. 466-475 ◽  
Author(s):  
Shih-Pin Chen ◽  
Jong-Ling Fuh ◽  
Ming-Yi Chung ◽  
Ying-Chao Lin ◽  
Yi-Chu Liao ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Risk Allele ◽  
Positive Association ◽  
Susceptibility Genes ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Significance Level ◽  
Genome Wide

Background Susceptibility genes for migraine, despite it being a highly prevalent and disabling neurological disorder, have not been analyzed in Asians by genome-wide association study (GWAS). Methods We conducted a two-stage case-control GWAS to identify susceptibility genes for migraine without aura in Han Chinese residing in Taiwan. In the discovery stage, we genotyped 1005 clinic-based Taiwanese migraine patients and 1053 population-based sex-matched controls using Axiom Genome-Wide CHB Array. In the replication stage, we genotyped 27 single-nucleotide polymorphisms with p < 10−4 in 1120 clinic-based migraine patients and 604 sex-matched normal controls by using Sequenom. Variants at LRP1, TRPM8, and PRDM, which have been replicated in Caucasians, were also genotyped. Results We identified a novel susceptibility locus (rs655484 in DLG2) that reached GWAS significance level for migraine risk in Han Chinese ( p = 1.45 × 10−12, odds ratio [OR] = 2.42), and also another locus (rs3781545in GFRA1) with suggestive significance ( p = 1.27 × 10−7, OR = 1.38). In addition, we observed positive association signals with a similar trend to the associations identified in Caucasian GWASs for rs10166942 in TRPM8 (OR = 1.33, 95% confidence interval [CI] = 1.14–1.54, Ppermutation = 9.99 × 10−5; risk allele: T) and rs1172113 in LRP1 (OR = 1.23, 95% CI = 1.04–1.45, Ppermutation = 2.9 × 10−2; risk allele: T). Conclusion The present study is the first migraine GWAS conducted in Han-Chinese and Asians. The newly identified susceptibility genes have potential implications in migraine pathogenesis. DLG2 is involved in glutamatergic neurotransmission, and GFRA1 encodes GDNF receptors that are abundant in CGRP-containing trigeminal neurons. Furthermore, positive association signals for TRPM8 and LRP1 suggest the possibility for common genetic contributions across ethnicities.

Association of multiple nucleotide variations in the pituitary glutaminyl cyclase gene QPC with low radial BMD in adult women.

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Linkage Disequilibrium ◽  
Multiple Regression ◽  
Genetic Variations ◽  
Strong Linkage Disequilibrium ◽  
Adult Women ◽  
Nucleotide Polymorphisms ◽  
Haplotype Estimation ◽  
Factors Affecting ◽  
Glutaminyl Cyclase ◽  
Strong Linkage

Correlation between 13 genetic variations of the glutaminyl-peptide cyclotransferase gene andadjusted aBMD was tested among 384 adult women. Among 13 variations with strong linkage disequilibrium,R54W showed a prominent association (p ? 0.0003), which was more striking when examined among 309 eldersubjects (&gt;50 years; p ? 0.0001). Contribution for postmenopausal bone loss was suggested.Introduction: Alterations in homeostatic regulation of estrogen through the hypothalamus-pituitary-gonadal axis(HPG axis) importantly affect the pathogenesis of osteoporosis. Osteoporosis-susceptibility genes have beenproposed in this hormonal axis, such as estrogen receptor genes and the gonadotropin-releasing hormone gene(GnRH). Here we report another example of genes: glutaminyl-peptide cyclotransferase gene (QPCT), an essentialmodifier of pituitary peptide hormones, including GnRH.Materials and Methods: Analyses of association of 13 single nucleotide polymorphisms (SNPs) at the QPCT locuswith adjusted areal BMD (adj-aBMD) were carried out among 384 adult women. Linkage disequilibrium (LD) wasanalyzed by haplotype estimation and calculation of D? and r2. Multiple regression analysis was applied forevaluating the combined effects of the variations.Results and Conclusions: LD analysis indicated strong linkage disequilibrium within the entire 30-kb region of theQPCT gene. Significant correlations were observed between the genotypes of the six SNPs and the radial adj-aBMD,among which R54W (nt ? 160C?T) presented the most prominent association (p ? 0.0003). Striking associationwas observed for these SNPs among the 309 subjects ?50 years of age (R54W, p ? 0.0001; ?1095T?C, p ?0.0002; ?1844C?T, p ? 0.0002). Multiple regression analyses indicated that multiple SNPs in the gene might actin combination to determine the radial adj-aBMD. These results indicate that genetic variations in QPCT are theimportant factors affecting the BMD of adult women that contribute to susceptibility for osteoporosis. The datashould provide new insight into the etiology of the disease and may suggest a new target to be considered duringtreatment.J Bone Miner

scholarly journals Comprehensive Genome-Wide Association Analysis Reveals the Genetic Basis of Root System Architecture in Soybean

2020 ◽  
Vol 11 ◽  
Author(s):  
Waldiodio Seck ◽  
Davoud Torkamaneh ◽  
François Belzile
Keyword(s):  
Root System ◽  
System Architecture ◽  
Phenotypic Variation ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Primary Root ◽  
Root System Architecture ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Genome Wide

Increasing the understanding genetic basis of the variability in root system architecture (RSA) is essential to improve resource-use efficiency in agriculture systems and to develop climate-resilient crop cultivars. Roots being underground, their direct observation and detailed characterization are challenging. Here, were characterized twelve RSA-related traits in a panel of 137 early maturing soybean lines (Canadian soybean core collection) using rhizoboxes and two-dimensional imaging. Significant phenotypic variation (P &lt; 0.001) was observed among these lines for different RSA-related traits. This panel was genotyped with 2.18 million genome-wide single-nucleotide polymorphisms (SNPs) using a combination of genotyping-by-sequencing and whole-genome sequencing. A total of 10 quantitative trait locus (QTL) regions were detected for root total length and primary root diameter through a comprehensive genome-wide association study. These QTL regions explained from 15 to 25% of the phenotypic variation and contained two putative candidate genes with homology to genes previously reported to play a role in RSA in other species. These genes can serve to accelerate future efforts aimed to dissect genetic architecture of RSA and breed more resilient varieties.

EXPRESS: Effect of genetic liability to visceral adiposity on stroke and its subtypes: a Mendelian randomization study

2021 ◽  
pp. 174749302110062
Author(s):  
Bin Yan ◽  
Jian Yang ◽  
Li Qian ◽  
Fengjie Gao ◽  
Ling Bai ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
Ischemic Stroke ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Visceral Adiposity ◽  
Large Artery ◽  
Nucleotide Polymorphisms ◽  
Genetic Liability ◽  
A Genome ◽  
Increased Risk

Background: Observational studies have found an association between visceral adiposity and stroke. Aims: The purpose of this study was to investigate the role and genetic effect of visceral adipose tissue (VAT) accumulation on stroke and its subtypes. Methods: In this two-sample Mendelian randomization (MR) study, genetic variants (221 single nucleotide polymorphisms; P<5×10-8) using as instrumental variables for MR analysis was obtained from a genome-wide association study (GWAS) of VAT. The outcome datasets for stroke and its subtypes were obtained from the MEGASTROKE consortium (up to 67,162 cases and 453,702 controls). MR standard analysis (inverse variance weighted method) was conducted to investigate the effect of genetic liability to visceral adiposity on stroke and its subtypes. Sensitivity analysis (MR-Egger, weighted median, MR-PRESSO) were also utilized to assess horizontal pleiotropy and remove outliers. Multi-variable MR analysis was employed to adjust potential confounders. Results: In the standard MR analysis, genetically determined visceral adiposity (per 1 SD) was significantly associated with a higher risk of stroke (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.21-1.41, P=1.48×10-11), ischemic stroke (OR 1.30; 95% CI 1.20-1.41, P=4.01×10-10), and large artery stroke (OR 1.49; 95% CI 1.22-1.83, P=1.16×10-4). The significant association was also found in sensitivity analysis and multi-variable MR analysis. Conclusions: Genetic liability to visceral adiposity was significantly associated with an increased risk of stroke, ischemic stroke, and large artery stroke. The effect of genetic susceptibility to visceral adiposity on the stroke warrants further investigation.

scholarly journals An artificial neural network approach integrating plasma proteomics and genetic data identifies PLXNA4 as a new susceptibility locus for pulmonary embolism

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Misbah Razzaq ◽  
Maria Jesus Iglesias ◽  
Manal Ibrahim-Kosta ◽  
Louisa Goumidi ◽  
Omar Soukarieh ◽  
...  
Keyword(s):  
Pulmonary Embolism ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Biological Traits ◽  
Nucleotide Polymorphisms ◽  
Ann Model ◽  
Neural Network Approach ◽  
A Genome ◽  
Increased Risk ◽  
Artificial Neural

AbstractVenous thromboembolism is the third common cardiovascular disease and is composed of two entities, deep vein thrombosis (DVT) and its potential fatal form, pulmonary embolism (PE). While PE is observed in ~ 40% of patients with documented DVT, there is limited biomarkers that can help identifying patients at high PE risk. To fill this need, we implemented a two hidden-layers artificial neural networks (ANN) on 376 antibodies and 19 biological traits measured in the plasma of 1388 DVT patients, with or without PE, of the MARTHA study. We used the LIME algorithm to obtain a linear approximate of the resulting ANN prediction model. As MARTHA patients were typed for genotyping DNA arrays, a genome wide association study (GWAS) was conducted on the LIME estimate. Detected single nucleotide polymorphisms (SNPs) were tested for association with PE risk in MARTHA. Main findings were replicated in the EOVT study composed of 143 PE patients and 196 DVT only patients. The derived ANN model for PE achieved an accuracy of 0.89 and 0.79 in our training and testing sets, respectively. A GWAS on the LIME approximate identified a strong statistical association peak (rs1424597: p = 5.3 × 10–7) at the PLXNA4 locus. Homozygote carriers for the rs1424597-A allele were then more frequently observed in PE than in DVT patients from the MARTHA (2% vs. 0.4%, p = 0.005) and the EOVT (3% vs. 0%, p = 0.013) studies. In a sample of 112 COVID-19 patients known to have endotheliopathy leading to acute lung injury and an increased risk of PE, decreased PLXNA4 levels were associated (p = 0.025) with worsened respiratory function. Using an original integrated proteomics and genetics strategy, we identified PLXNA4 as a new susceptibility gene for PE whose exact role now needs to be further elucidated.

scholarly journals Genome-wide association study in almost 195,000 individuals identifies 50 previously unidentified genetic loci for eye color

2021 ◽  
Vol 7 (11) ◽  
pp. eabd1239
Author(s):  
Mark Simcoe ◽  
Ana Valdes ◽  
Fan Liu ◽  
Nicholas A. Furlotte ◽  
David M. Evans ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Color Variation ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Melanin Pigmentation ◽  
Eye Color ◽  
Human Eye ◽  
Genome Wide ◽  
Genomic Regions

Human eye color is highly heritable, but its genetic architecture is not yet fully understood. We report the results of the largest genome-wide association study for eye color to date, involving up to 192,986 European participants from 10 populations. We identify 124 independent associations arising from 61 discrete genomic regions, including 50 previously unidentified. We find evidence for genes involved in melanin pigmentation, but we also find associations with genes involved in iris morphology and structure. Further analyses in 1636 Asian participants from two populations suggest that iris pigmentation variation in Asians is genetically similar to Europeans, albeit with smaller effect sizes. Our findings collectively explain 53.2% (95% confidence interval, 45.4 to 61.0%) of eye color variation using common single-nucleotide polymorphisms. Overall, our study outcomes demonstrate that the genetic complexity of human eye color considerably exceeds previous knowledge and expectations, highlighting eye color as a genetically highly complex human trait.

scholarly journals Genome-Wide Association Study (GWAS) for Examining the Genomics Controlling Prickle Production in Red Raspberry (Rubus idaeus L.)

Agronomy ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 27
Author(s):  
Archana Khadgi ◽  
Courtney A. Weber
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genomic Region ◽  
Rubus Idaeus ◽  
Genome Wide Association ◽  
Nucleotide Polymorphisms ◽  
Red Raspberry ◽  
Genome Wide ◽  
A Genome ◽  
Genotype By Sequencing

Red raspberry (Rubus idaeus L.) is an expanding high-value berry crop worldwide. The presence of prickles, outgrowths of epidermal tissues lacking vasculature, on the canes, petioles, and undersides of leaves complicates both field management and harvest. The utilization of cultivars with fewer prickles or prickle-free canes simplifies production. A previously generated population segregating for prickles utilizing the s locus between the prickle-free cultivar Joan J (ss) and the prickled cultivar Caroline (Ss) was analyzed to identify the genomic region associated with prickle development in red raspberry. Genotype by sequencing (GBS) was combined with a genome-wide association study (GWAS) using fixed and random model circulating probability unification (FarmCPU) to analyze 8474 single nucleotide polymorphisms (SNPs) and identify significant markers associated with the prickle-free trait. A total of four SNPs were identified on chromosome 4 that were associated with the phenotype and were located near or in annotated genes. This study demonstrates how association genetics can be used to decipher the genetic control of important horticultural traits in Rubus, and provides valuable information about the genomic region and potential genes underlying the prickle-free trait.

scholarly journals Genome-Wide Association Analysis of Growth Curve Parameters in Chinese Simmental Beef Cattle

Animals ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 192
Author(s):  
Xinghai Duan ◽  
Bingxing An ◽  
Lili Du ◽  
Tianpeng Chang ◽  
Mang Liang ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Candidate Genes ◽  
Growth Curve ◽  
Growth And Development ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Coefficient Of Determination ◽  
Nucleotide Polymorphisms ◽  
Genome Wide ◽  
A Genome

The objective of the present study was to perform a genome-wide association study (GWAS) for growth curve parameters using nonlinear models that fit original weight–age records. In this study, data from 808 Chinese Simmental beef cattle that were weighed at 0, 6, 12, and 18 months of age were used to fit the growth curve. The Gompertz model showed the highest coefficient of determination (R2 = 0.954). The parameters’ mature body weight (A), time-scale parameter (b), and maturity rate (K) were treated as phenotypes for single-trait GWAS and multi-trait GWAS. In total, 9, 49, and 7 significant SNPs associated with A, b, and K were identified by single-trait GWAS; 22 significant single nucleotide polymorphisms (SNPs) were identified by multi-trait GWAS. Among them, we observed several candidate genes, including PLIN3, KCNS3, TMCO1, PRKAG3, ANGPTL2, IGF-1, SHISA9, and STK3, which were previously reported to associate with growth and development. Further research for these candidate genes may be useful for exploring the full genetic architecture underlying growth and development traits in livestock.

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