scholarly journals A genome-wide association study of quantitative computed tomographic emphysema in Korean populations

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sooim Sin ◽  
Hye-Mi Choi ◽  
Jiwon Lim ◽  
Jeeyoung Kim ◽  
So Hyeon Bak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Candidate Snps ◽  
Copd Patients ◽  
Genome Wide ◽  
A Genome ◽  
Novel Snp

AbstractEmphysema is an important feature of chronic obstructive pulmonary disease (COPD). Genetic factors likely affect emphysema pathogenesis, but this question has predominantly been studied in those of European ancestry. In this study, we sought to determine genetic components of emphysema severity and characterize the potential function of the associated loci in Korean population. We performed a genome-wide association study (GWAS) on quantitative emphysema in subjects with or without COPD from two Korean COPD cohorts. We investigated the functional consequences of the loci using epigenetic annotation and gene expression data. We also compared our GWAS results with an epigenome-wide association study and previous differential gene expression analysis. In total, 548 subjects (476 [86.9%] male) including 514 COPD patients were evaluated. We identified one genome-wide significant SNP (P < 5.0 × 10–8), rs117084279, near PIBF1. We identified an additional 57 SNPs (P < 5.0 × 10–6) associated with emphysema in all subjects, and 106 SNPs (P < 5.0 × 10–6) in COPD patients. Of these candidate SNPs, 2 (rs12459249, rs11667314) near CYP2A6 were expression quantitative trait loci in lung tissue and a SNP (rs11214944) near NNMT was an expression quantitative trait locus in whole blood. Of note, rs11214944 was in linkage disequilibrium with variants in enhancer histone marks in lung tissue. Several genes near additional SNPs were identified in our previous EWAS study with nominal level of significance. We identified a novel SNP associated with quantitative emphysema on CT. Including the novel SNP, several candidate SNPs in our study may provide clues to the genetic etiology of emphysema in Asian populations. Further research and validation of the loci will help determine the genetic factors for the development of emphysema.

scholarly journals Gene-Based Tests of a Genome-Wide Association Study Dataset Highlight Novel Multiple Sclerosis Risk Genes

2021 ◽  
Vol 15 ◽  
Author(s):  
He Li ◽  
Xiaodan Hou ◽  
Yan Liang ◽  
Fang Xu ◽  
Xiyue Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Healthy Controls ◽  
Risk Genes ◽  
Gwas Dataset ◽  
Genome Wide ◽  
A Genome

Multiple sclerosis (MS) is an autoimmune disorder influenced by genetic and environmental factors. Many studies have provided insights into genetic factors’ contribution to MS via large-scale genome-wide association study (GWAS) datasets. However, genetic variants identified to date do not adequately explain genetic risks for MS. This study hypothesized that novel MS risk genes could be identified by analyzing the MS-GWAS dataset using gene-based tests. We analyzed a GWAS dataset consisting of 9,772 MS cases and 17,376 healthy controls of European descent. We performed gene-based tests of 464,357 autosomal single nucleotide polymorphisms (SNPs) using two methods (PLINK and VEGAS2) and identified 28 shared genes satisfied p-value &lt; 4.56 × 10–6. In further gene expression analysis, ten of the 28 genes were significantly differentially expressed in the MS case-control gene expression omnibus (GEO) database. GALC and HLA-DOB showed the most prominent differences in gene expression (two- and three-fold, respectively) between MS patients and healthy controls. In conclusion, our results reveal more information about MS hereditary characteristics and provide a basis for further studies.

scholarly journals A Genome-Wide Association Study Identifying SVEP1 Variant as a Predictor of Response to Tolvaptan for Cirrhotic Ascites

2021 ◽  
Author(s):  
Yasuhito Tanaka ◽  
Hideto Kawaratani ◽  
Hiromi Sawai ◽  
Masaya Onishi ◽  
Tomomi Kogiso ◽  
...  
Keyword(s):  
Association Study ◽  
Failure Probability ◽  
Genome Wide Association Study ◽  
Replication Study ◽  
Genome Wide Association ◽  
Candidate Snps ◽  
Genome Wide ◽  
A Genome ◽  
Study Results ◽  
V2 Receptor

Abstract Background and Aims: Tolvaptan, an orally active vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan’s efficacy for patients with hepatic ascites. Methods: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; > 1.5 kg decrease of BW) were included in the GWAS and replication study. Results: GWAS showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 x 10− 8). Univariate and multivariate analyses showed that blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 1.03, p = 0.02 and OR = 4.24, p < 0.0001, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (= exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. Conclusion: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

scholarly journals The combination of a genome-wide association study of lymphocyte count and analysis of gene expression data reveals novel asthma candidate genes

2012 ◽  
Vol 21 (9) ◽  
pp. 2111-2123 ◽  
Author(s):  
Darren A. Cusanovich ◽  
Christine Billstrand ◽  
Xiang Zhou ◽  
Claudia Chavarria ◽  
Sherryl De Leon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Candidate Genes ◽  
Gene Expression Data ◽  
Lymphocyte Count ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Expression Data ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study identifies genetic factors that modify age at onset in Machado-Joseph disease

2019 ◽  
Author(s):  
Fulya Akçimen ◽  
Sandra Martins ◽  
Calwing Liao ◽  
Cynthia V. Bourassa ◽  
Hélène Catoire ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Age At Onset ◽  
Cag Repeat ◽  
Genome Wide Association ◽  
Modifying Factors ◽  
Genome Wide ◽  
A Genome ◽  
Machado Joseph Disease

AbstractMachado-Joseph disease (MJD/SCA3) is the most common form of dominantly inherited ataxia worldwide. The disorder is caused by an expanded CAG repeat in the ATXN3 gene. Past studies have revealed that the length of the expansion partly explains the disease age at onset (AO) variability of MJD, which is confirmed in this study. Using a total of 786 MJD patients from five different geographical origins, a genome-wide association study (GWAS) was conducted to identify additional AO modifying factors that could explain some of the residual AO variability. We identified nine suggestively associated loci (P < 1 × 10−5). These loci were enriched for genes involved in vesicle transport, olfactory signaling, and synaptic pathways. Furthermore, associations between AO and the TRIM29 and RAG genes suggests that DNA repair mechanisms might be implicated in MJD pathogenesis. Our study demonstrates the existence of several additional genetic factors, along with CAG expansion, that may lead to a better understanding of the genotype-phenotype correlation in MJD.

scholarly journals Dissection of the Genetic Basis of Rice Panicle Architecture Using a Genome-wide Association Study

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Shaoxing Bai ◽  
Jun Hong ◽  
Ling Li ◽  
Su Su ◽  
Zhikang Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Candidate Genes ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Panicle Length ◽  
Genome Wide ◽  
A Genome ◽  
Panicle Architecture

AbstractPanicle architecture is one of the major factors influencing productivity of rice crops. The regulatory mechanisms underlying this complex trait are still unclear and genetic resources for rice breeders to improve panicle architecture are limited. Here, we have performed a genome-wide association study (GWAS) to analyze and identify genetic determinants underlying three panicle architecture traits. A population of 340 rice accessions from the 3000 Rice Genomes Project was phenotyped for panicle length, primary panicle number and secondary branch number over two years; GWAS was performed across the whole panel, and also across the japonica and indica sub-panels. A total of 153 quantitative trait loci (QTLs) were detected, of which 5 were associated with multiple traits, 8 were unique to either indica or japonica sub-panels, while 37 QTLs were stable across both years. Using haplotype and expression analysis, we reveal that genetic variations in the OsSPL18 promoter significantly affect gene expression and correlate with panicle length phenotypes. Three new candidate genes with putative roles in determining panicle length were also identified. Haplotype analysis of OsGRRP and LOC_Os03g03480 revealed high association with panicle length variation. Gene expression of DSM2, involved in abscisic acid biosynthesis, was up-regulated in long panicle accessions. Our results provide valuable information and resources for further unravelling the genetic basis determining rice panicle architecture. Identified candidate genes and molecular markers can be used in marker-assisted selection to improve rice panicle architecture through molecular breeding.

A genome-wide association study of global gene expression

2007 ◽  
Vol 39 (10) ◽  
pp. 1202-1207 ◽  
Author(s):  
Anna L Dixon ◽  
Liming Liang ◽  
Miriam F Moffatt ◽  
Wei Chen ◽  
Simon Heath ◽  
...  
Keyword(s):  
Gene Expression ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Global Gene Expression ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study identifies ERBB4 on 2q34 as a novel locus associated with sperm motility in Japanese men

2018 ◽  
Vol 55 (6) ◽  
pp. 415-421 ◽  
Author(s):  
Youichi Sato ◽  
Atsushi Tajima ◽  
Takehiro Sato ◽  
Shiari Nozawa ◽  
Miki Yoshiike ◽  
...  
Keyword(s):  
Association Study ◽  
Sperm Motility ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Human Populations ◽  
Motile Sperm ◽  
Japanese Men ◽  
Genome Wide ◽  
A Genome

BackgroundThe decrease in sperm motility has a potent influence on fertilisation. Sperm motility, represented as the percentage of motile sperm in ejaculated sperms, is influenced by lifestyle habits or environmental factors and by inherited factors. However, genetic factors contributing to individual differences in sperm motility remain unclear. To identify genetic factors that influence human sperm motility, we performed a genome-wide association study (GWAS) of sperm motility.MethodsA two-stage GWAS was conducted using 811 Japanese men in a discovery stage, followed by a replication study using an additional 779 Japanese men.ResultsIn the two-staged GWAS, a single nucleotide polymorphism rs3791686 in the intron of gene for erb-b2 receptor tyrosine kinase 4 (ERBB4) on chromosome 2q34 was identified as a novel locus for sperm motility, as evident from the discovery and replication results using meta-analysis (β=−4.01, combined P=5.40×10−9).ConclusionsTogether with the previous evidence that Sertoli cell-specific Erbb4-knockout mice display an impaired ability to produce motile sperm, this finding provides the first genetic evidence for further investigation of the genome-wide significant association at the ERBB4 locus in larger studies across diverse human populations.

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