scholarly journals A genome-wide association study of deviated nasal septum using UK Biobank cohort

2020 ◽  
Author(s):  
Li Liu ◽  
CuiYan Wu ◽  
Xiaoxia Dai ◽  
Yan Wen ◽  
Shiqiang Cheng ◽  
...  
Keyword(s):  
Association Study ◽  
Nasal Septum ◽  
Genome Wide Association Study ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Genetic Mechanism ◽  
Uk Biobank ◽  
Deviated Nasal Septum ◽  
Gene Sets ◽  
Genome Wide

Abstract Background Deviated nasal septum (DNS) is a common otolaryngology disease. The genetic mechanism underlying DNS remains largely unknown. Methods Totally, 2, 978 DNS patients and 2,978 randomly selected controls from the UK biobank were used in this study. Genotyping was done using the Affymetrix UK BiLEVE Axiom or UK Biobank Axiom array. Genome-wide association study (GWAS) was performed by PLINK 2.0, using age, sex, population structure PC1, PC2 and PC3 as covariates. eQTLs analysis and gene set enrichment analysis (GSEA) were also performed to explore the functional relevance of identified loci with DNS. Results GWAS identified multiple candidate genetic loci for DNS, such as rs75651247 located in DLGAP1 (β=-5.3398, P=9.31×10-8), rs141366706 located in CCND3 (β=-4.7036, P=2.56×10-6), rs76606504 located in FAF1 (β=-4.5013, P=6.76×10-6), and rs142537880 located in SVIL (β= 4.4336, P=9.27×10-6). GSEA detected multiple DNS associated gene sets or pathways, such as KEGG_CALCIUM_SIGNALING_PATHWAY (FDR=3.35×10-3, P=5×10-5) and DAVICIONI_TARGETS_OF_PAX_FOXO1_FUSIONS_UP (FDR=1.60×10-3, P=5×10-5). Conclusions Our study reported multiple candidate genes and gene sets for DNS, providing novel clues for understanding the genetic mechanism of DNS.

scholarly journals Genome-Wide Association Analysis Identified ANXA1 Associated with Shoulder Impingement Syndrome in UK Biobank Samples

2020 ◽  
Vol 10 (9) ◽  
pp. 3279-3284
Author(s):  
Bolun Cheng ◽  
Yujie Ning ◽  
Chujun Liang ◽  
Ping Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Enrichment Analysis ◽  
Impingement Syndrome ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Genetic Mechanism ◽  
Shoulder Impingement Syndrome ◽  
Uk Biobank ◽  
Shoulder Impingement ◽  
Genome Wide

Abstract Shoulder impingement syndrome (SIS) is a common shoulder disorder with unclear genetic mechanism. In this study, Genome-wide Association Study (GWAS) was conducted to identify the candidate loci associated with SIS by using the UK Biobank samples (including 3,626 SIS patients and 3,626 control subjects). Based on the GWAS results, gene set enrichment analysis was further performed to detect the candidate gene ontology and pathways associated with SIS. We identified multiple risk loci associated with SIS, such as rs750968 (P = 4.82 × 10−8), rs754832 (P = 4.83 × 10−8) and rs1873119 (P = 6.39 × 10−8) of ANXA1 gene. Some candidate pathways have been identified related to SIS, including those linked to infection response and hypoxia, “ZHOU_INFLAMMATORY_RESPONSE_FIMA_DN” (P = 0.012) and “MANALO_HYPOXIA_UP” (P = 5.00 × 10−5). Our results provide novel clues for understanding the genetic mechanism of SIS.

scholarly journals Genome-wide association study of appendicular lean mass in UK Biobank cohort

2019 ◽  
Author(s):  
Yu-Fang Pei ◽  
Yao-Zhong Liu ◽  
Xiao-Lin Yang ◽  
Hong Zhang ◽  
Gui-Juan Feng ◽  
...  
Keyword(s):  
Association Study ◽  
Lean Mass ◽  
Genetic Basis ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Phenotypic Variance ◽  
Uk Biobank ◽  
Appendicular Lean Mass ◽  
Gene Sets ◽  
Genome Wide

AbstractLean body mass (LBM), an important physiological measure, has a strong genetic determination. To clarify its genetic basis, a large-scale genome-wide association study (GWAS) of appendicular lean mass (ALM) was conducted in 450,580 UK Biobank subjects. A total of 717 variants (p<5×10−9) from 561 loci were identified, which were replicated across genders (achieving p<5×10−5 in both genders). The identified variants explained ~11% phenotypic variance, accounting for one quarter of the total ~40% GWAS-attributable heritability. The identified variants were enriched in gene sets related to musculoskeletal and connective tissue development. Of interest are several genes, including ADAMTS3, PAM, SMAD3 and MEF2C, that either contain multiple significant variants or serve as the hub genes of the associated gene sets. Polygenic score prediction based on the associated variants was able to distinguish subjects of high from low ALM. Overall, our results offered significant findings on the genetic basis of lean mass through an extraordinarily large sample GWAS. The findings are important to not only lean mass per se but also other complex diseases, such as type 2 diabetes and fracture, as our Mendelian randomization analysis showed that ALM is a protective factor for these two diseases.

scholarly journals Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Helena R. R. Wells ◽  
Fatin N. Zainul Abidin ◽  
Maxim B. Freidin ◽  
Frances M. K. Williams ◽  
Sally J. Dawson
Keyword(s):  
Association Study ◽  
Molecular Mechanisms ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Significance Threshold ◽  
Genome Wide ◽  
Final Sample ◽  
Close Proximity ◽  
Repressor Complex

AbstractTinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case–control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E−08), rs4900545 (p = 1.8E−08) and 14:103042287_CT_C (p = 3.50E−08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E−06.

scholarly journals Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank

PLoS Genetics ◽  
2021 ◽  
Vol 17 (4) ◽  
pp. e1009428
Author(s):  
Keira J. A. Johnston ◽  
Joey Ward ◽  
Pradipta R. Ray ◽  
Mark J. Adams ◽  
Andrew M. McIntosh ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Sex Differences ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Chronic Widespread Pain ◽  
Genome Wide Association ◽  
System Component ◽  
Widespread Pain ◽  
Uk Biobank ◽  
Genome Wide

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception.

scholarly journals Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

2021 ◽  
Author(s):  
Mengyao Yu ◽  
Sergiy Kyryachenko ◽  
Stephanie Debette ◽  
Philippe Amouyel ◽  
Jean-Jacques Schott ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Cardiac Development ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
Uk Biobank ◽  
Additional Risk ◽  
Genome Wide ◽  
The Uk

Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study have identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. Methods: We reanalyzed 1007/479 cases from the MVP-France study, 1469/862 controls from the MVP-Nantes study for reimputation genotypes using HRC and TOPMed panels. We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used FUMA for post-genome-wide association study annotations and MAGMA for gene-based and gene-set analyses. Results: We found TOPMed imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1 . We identified an additional risk locus on Chr1 ( SYT2 ) and 2 suggestive risk loci on chr8 ( MSRA ) and chr19 ( FBXO46 ), all driven by common variants. Gene-based association using MAGMA revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. Conclusions: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.

scholarly journals Haplotype-Based Genome-Wide Association Study and Identification of Candidate Genes Associated with Carcass Traits in Hanwoo Cattle

Genes ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 551
Author(s):  
Swati Srivastava ◽  
Krishnamoorthy Srikanth ◽  
Sohyoung Won ◽  
Ju-Hwan Son ◽  
Jong-Eun Park ◽  
...  
Keyword(s):  
Association Study ◽  
Candidate Genes ◽  
Haplotype Block ◽  
Genome Wide Association Study ◽  
Carcass Traits ◽  
Gene Set Enrichment Analysis ◽  
Genome Wide Association ◽  
Haplotype Blocks ◽  
Genome Wide ◽  
Hanwoo Cattle

Hanwoo, is the most popular native beef cattle in South Korea. Due to its extensive popularity, research is ongoing to enhance its carcass quality and marbling traits. In this study we conducted a haplotype-based genome-wide association study (GWAS) by constructing haplotype blocks by three methods: number of single nucleotide polymorphisms (SNPs) in a haplotype block (nsnp), length of genomic region in kb (Len) and linkage disequilibrium (LD). Significant haplotype blocks and genes associated with them were identified for carcass traits such as BFT (back fat thickness), EMA (eye Muscle area), CWT (carcass weight) and MS (marbling score). Gene-set enrichment analysis and functional annotation of genes in the significantly-associated loci revealed candidate genes, including PLCB1 and PLCB4 present on BTA13, coding for phospholipases, which might be important candidates for increasing fat deposition due to their role in lipid metabolism and adipogenesis. CEL (carboxyl ester lipase), a bile-salt activated lipase, responsible for lipid catabolic process was also identified within the significantly-associated haplotype block on BTA11. The results were validated in a different Hanwoo population. The genes and pathways identified in this study may serve as good candidates for improving carcass traits in Hanwoo cattle.

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