Decomposing genomic variance using information from GWA, GWE and eQTL analysis

2015 ◽  
Vol 47 (2) ◽  
pp. 165-173 ◽  
Author(s):  
A. Ehsani ◽  
L. Janss ◽  
D. Pomp ◽  
P. Sørensen
Keyword(s):  
Eqtl Analysis ◽  
Genomic Variance

scholarly journals Integrative genomics reveals paths to sex dimorphism in Salix purpurea L

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Brennan Hyden ◽  
Craig H. Carlson ◽  
Fred E. Gouker ◽  
Jeremy Schmutz ◽  
Kerrie Barry ◽  
...  
Keyword(s):  
Gene Expression ◽  
Sex Determination ◽  
Bisulfite Sequencing ◽  
Epigenetic Modification ◽  
Small Rna Sequencing ◽  
Regulation Of Transcription ◽  
Eqtl Analysis ◽  
Sex Dimorphism ◽  
Network Analyses ◽  
Salix Purpurea

AbstractSex dimorphism and gene expression were studied in developing catkins in 159 F2 individuals from the bioenergy crop Salix purpurea, and potential mechanisms and pathways for regulating sex development were explored. Differential expression, eQTL, bisulfite sequencing, and network analysis were used to characterize sex dimorphism, detect candidate master regulator genes, and identify pathways through which the sex determination region (SDR) may mediate sex dimorphism. Eleven genes are presented as candidates for master regulators of sex, supported by gene expression and network analyses. These include genes putatively involved in hormone signaling, epigenetic modification, and regulation of transcription. eQTL analysis revealed a suite of transcription factors and genes involved in secondary metabolism and floral development that were predicted to be under direct control of the sex determination region. Furthermore, data from bisulfite sequencing and small RNA sequencing revealed strong differences in expression between males and females that would implicate both of these processes in sex dimorphism pathways. These data indicate that the mechanism of sex determination in Salix purpurea is likely different from that observed in the related genus Populus. This further demonstrates the dynamic nature of SDRs in plants, which involves a multitude of mechanisms of sex determination and a high rate of turnover.

scholarly journals A Genome-Wide Association Study for Hypertensive Kidney Disease in Korean Men

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 751
Author(s):  
Hye-Rim Kim ◽  
Hyun-Seok Jin ◽  
Yong-Bin Eom
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Integrated Analysis ◽  
Eqtl Analysis ◽  
Strong Linkage Disequilibrium ◽  
Genome Wide ◽  
A Genome

Hypertension is one of the major risk factors for chronic kidney disease (CKD), and the coexistence of hypertension and CKD increases morbidity and mortality. Although many genetic factors have been identified separately for hypertension and kidney disease, studies specifically focused on hypertensive kidney disease (HKD) have been rare. Therefore, this study aimed to identify loci or genes associated with HKD. A genome-wide association study (GWAS) was conducted using two Korean cohorts, the Health Examinee (HEXA) and Korean Association REsource (KARE). Consequently, 19 single nucleotide polymorphisms (SNPs) were found to be significantly associated with HKD in the discovery and replication phases (p < 5 × 10−8, p < 0.05, respectively). We further analyzed HKD-related traits such as the estimated glomerular filtration rate (eGFR), creatinine, blood urea nitrogen (BUN), systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the 14q21.2 locus, which showed a strong linkage disequilibrium (LD). Expression quantitative trait loci (eQTL) analysis was also performed to determine whether HKD-related SNPs affect gene expression changes in glomerular and arterial tissues. The results suggested that the FANCM gene may affect the development of HKD through an integrated analysis of eQTL and GWAS and was the most significantly associated candidate gene. Taken together, this study indicated that the FANCM gene is involved in the pathogenesis of HKD. Additionally, our results will be useful in prioritizing other genes for further experiments.

scholarly journals Variation in the SERPINA6/SERPINA1 locus alters morning plasma cortisol, hepatic corticosteroid binding globulin expression, gene expression in peripheral tissues, and risk of cardiovascular disease

2021 ◽  
Author(s):  
Andrew A. Crawford ◽  
◽  
Sean Bankier ◽  
Elisabeth Altmaier ◽  
Catriona L. K. Barnes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Genetic Variants ◽  
Plasma Cortisol ◽  
Statistical Power ◽  
Mendelian Randomisation ◽  
Eqtl Analysis ◽  
Causative Role ◽  
Peripheral Tissues ◽  
Corticosteroid Binding Globulin

AbstractThe stress hormone cortisol modulates fuel metabolism, cardiovascular homoeostasis, mood, inflammation and cognition. The CORtisol NETwork (CORNET) consortium previously identified a single locus associated with morning plasma cortisol. Identifying additional genetic variants that explain more of the variance in cortisol could provide new insights into cortisol biology and provide statistical power to test the causative role of cortisol in common diseases. The CORNET consortium extended its genome-wide association meta-analysis for morning plasma cortisol from 12,597 to 25,314 subjects and from ~2.2 M to ~7 M SNPs, in 17 population-based cohorts of European ancestries. We confirmed the genetic association with SERPINA6/SERPINA1. This locus contains genes encoding corticosteroid binding globulin (CBG) and α1-antitrypsin. Expression quantitative trait loci (eQTL) analyses undertaken in the STARNET cohort of 600 individuals showed that specific genetic variants within the SERPINA6/SERPINA1 locus influence expression of SERPINA6 rather than SERPINA1 in the liver. Moreover, trans-eQTL analysis demonstrated effects on adipose tissue gene expression, suggesting that variations in CBG levels have an effect on delivery of cortisol to peripheral tissues. Two-sample Mendelian randomisation analyses provided evidence that each genetically-determined standard deviation (SD) increase in morning plasma cortisol was associated with increased odds of chronic ischaemic heart disease (0.32, 95% CI 0.06–0.59) and myocardial infarction (0.21, 95% CI 0.00–0.43) in UK Biobank and similarly in CARDIoGRAMplusC4D. These findings reveal a causative pathway for CBG in determining cortisol action in peripheral tissues and thereby contributing to the aetiology of cardiovascular disease.

Abstract 12905: Gene Expression and Expression Quantifying Trait Loci Analysis of Left Atrium of Patients With Post-operative Atrial Fibrillation

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Martin I Sigurdsson ◽  
Mahyar Heydarpour ◽  
Louis Saddic ◽  
Tzuu-Wang Chang ◽  
Stanton K Shernan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Atrial Fibrillation ◽  
Left Atrium ◽  
High Throughput ◽  
Specific Gene ◽  
Eqtl Analysis ◽  
Gene Variants ◽  
Nucleotide Polymorphisms ◽  
Novel Genes ◽  
Trait Loci

Introduction: The majority of information on the genetic background of atrial fibrillation (AF) results from genomic DNA variant analysis without consideration of tissue expression. Hypothesis: Analysis of tissue-specific gene expression in left atrium (LA) can further understanding of the molecular mechanism of identified AF risk variants, and identify novel genes and gene variants associated with AF. Methods: We isolated mRNA from samples of the LA free wall taken during mitral valve surgery in 62 Caucasian individuals. Gene expression in the LA was compared between patients who did and did not have post-operative AF (poAF) using high-throughput RNA expression. Using genotypes of 1.4 million single nucleotide polymorphisms (SNP) we performed cis expression quantifying trait loci (eQTL) analysis, correlating gene expression of each gene with the genotypes of adjacent (<1Mbp) SNPs. Results: We identified 23 differentially expressed genes in the LA of patients with poAF, including three potassium channel genes (KCNA7, KCNH8 and KCNK17). The largest expression difference was in LOC645323, a long non-coding RNA. The expression of PITX2, ZFHX3 and KCNN3, previously shown to be associated with AF, did not differ between patients with and without poAF. We identified 12,476 cis eQTL relationships in the LA, several of those included genetic regions and genes previously associated with AF. We confirmed an eQTL relationship between rs3744029 genotype and the expression of MYOZ1. Furthermore we describe a novel eQTL relationship between rs6795970 genotype and the expression of the SCN10A gene. Conclusions: We have analysed the human LA expression via high-throughput RNA sequencing, and identified novel genes and gene variants likely involved in the molecular pathophysiology of AF.

scholarly journals WNT3A rs752107(C > T) Polymorphism Is Associated With an Increased Risk of Essential Hypertension and Related Cardiovascular Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Huan Ren ◽  
Jian-Quan Luo ◽  
Fan Ouyang ◽  
Li Cheng ◽  
Xiao-Ping Chen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Essential Hypertension ◽  
Signaling Pathway ◽  
Genetic Variant ◽  
Eqtl Analysis ◽  
Cardiovascular Development ◽  
Genomic Variants ◽  
Increased Risk ◽  
First Time

Essential Hypertension (EH) results in the burden of cardiovascular disease (CVD) such as Heart Failure (HF) and Ischemic Stroke (IS). A rapidly emerging field involving the role of Wnt/β-catenin signaling pathway in cardiovascular development and dysfunction has recently drawn extensive attention. In the present study, we conducted a genetic association between genomic variants in Wnt/β-catenin signaling pathway and EH, HF, IS. A total of 95 SNPs in 12 Wnt signaling genes (WNT3A, WNT3, WNT4, DKK1, DKK2, LRP5, LRP6, CTNNB1, APC, FZD1, FRZB, SFRP1) were genotyped in 1,860 participants (440 patients with EH, 535 patients with HF, 421 patients with IS and 464 normal control subjects) using Sequenom MassArray technology. WNT3A rs752107(C &gt; T) was strongly associated with an increased risk of EH, HF and IS. Compared with WNT3A rs752107 CC genotype, the CT genotype carriers had a 48% increased risk of EH (OR = 1.48, 95% CI = 1.12–1.96, P = 0.006), the TT genotype conferred a 139% increased risk of EH (OR = 2.39, 95% CI = 1.32–4.34, P = 0.003). Regarding HF and IS, the risk of HF in the T allele carriers (CT + TT) was nearly increased by 58% (OR = 1.58, 95% CI = 1.22–2.04, P = 4.40 × 10−4) and the risk of IS was increased by 37% (OR = 1.37, 95% CI = 1.04–1.79, P = 0.025). Expression quantitative trait loci (eQTL) analysis indicated that rs752107 C allele corresponded to a significant reduction of WNT3A expression. We described a genetic variant of WNT3A rs752107 in Wnt/β-catenin signaling strongly associated with the risk of EH, HF and IS for the first time.

scholarly journals Programmed Death Ligand 2 Gene Polymorphisms Are Associated With Lung Adenocarcinoma Risk in Female Never-Smokers

2021 ◽  
Vol 11 ◽  
Author(s):  
Sheng-Kai Liang ◽  
Li-Hsin Chien ◽  
Gee-Chen Chang ◽  
Ying-Huang Tsai ◽  
Wu-Chou Su ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Pulmonary Tuberculosis ◽  
Lung Adenocarcinoma ◽  
Genome Wide Association Study ◽  
Lung Cancer Screening ◽  
Tuberculosis Infection ◽  
Eqtl Analysis ◽  
Nucleotide Polymorphisms ◽  
Programmed Death ◽  
Never Smokers

ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p &lt; 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.

scholarly journals Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue

2020 ◽  
Author(s):  
Devanshi Patel ◽  
Xiaoling Zhang ◽  
John J. Farrell ◽  
Jaeyoon Chung ◽  
Thor D. Stein ◽  
...  
Keyword(s):  
Gene Expression ◽  
Quantitative Trait ◽  
Expression Patterns ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Eqtl Analysis ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.

scholarly journals Novel KITLG/SCF regulatory variants are associated with lung function in African American children with asthma

2020 ◽  
Author(s):  
Angel CY Mak ◽  
Satria Sajuthi ◽  
Jaehyun Joo ◽  
Shujie Xiao ◽  
Patrick M Sleiman ◽  
...  
Keyword(s):  
African American ◽  
Lung Function ◽  
Genetic Association ◽  
Interaction Analysis ◽  
Whole Genome Sequencing Data ◽  
African American Children ◽  
Eqtl Analysis ◽  
Sequencing Data ◽  
Children With Asthma ◽  
American Children

ABSTRACTBaseline lung function, quantified as forced expiratory volume in the first second of exhalation (FEV1), is a standard diagnostic criterion used by clinicians to identify and classify lung diseases. Using whole genome sequencing data from the National Heart, Lung, and Blood Institute TOPMed project, we identified a novel genetic association with FEV1 on chromosome 12 in 867 African American children with asthma (p = 1.26 × 10−8, β = 0.302). Conditional analysis within 1 Mb of the tag signal (rs73429450) yielded one major and two other weaker independent signals within this peak. We explored statistical and functional evidence for all variants in linkage disequilibrium with the three independent signals and yielded 9 variants as the most likely candidates responsible for the association with FEV1. Hi-C data and eQTL analysis demonstrated that these variants physically interacted with KITLG (aka SCF) and their minor alleles were associated with increased expression of KITLG gene in nasal epithelial cells. Gene-by-air-pollution interaction analysis found that the candidate variant rs58475486 interacted with past-year SO2 exposure (p = 0.003, β = 0.32). This study identified a novel protective genetic association with FEV1, possibly mediated through KITLG, in African American children with asthma.

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