scholarly journals Transcriptome-wide association study identified candidate genes associated with gut microbiota

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chuyu Pan ◽  
Yujie Ning ◽  
Yumeng Jia ◽  
Shiqiang Cheng ◽  
Yan Wen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Association Study ◽  
Candidate Genes ◽  
Sigmoid Colon ◽  
Transverse Colon ◽  
Large Scale ◽  
Data Sets ◽  
Study Results ◽  
Regulated Gene Expression ◽  
Functional Analyses

Abstract Background Gut microbiota is closely associated with host health and disease occurrence. Host genetic factor plays an important role in shaping gut microbial communities. The specific mechanism of host-regulated gene expression affecting gut microbiota has not been elucidated yet. Here we conducted a transcriptome-wide association study (TWAS) for gut microbiota by leveraging expression imputation from large-scale GWAS data sets. Results TWAS detected multiple tissue-specific candidate genes for gut microbiota, such as FUT2 for genus Bifidobacterium in transverse colon (PPERM.ANL = 1.68 × 10–3) and SFTPD for an unclassified genus of Proteobacteria in transverse colon (PPERM.ANL = 5.69 × 10–3). Fine mapping replicated 3 candidate genes in TWAS, such as HELLS for Streptococcus (PIP = 0.685) in sigmoid colon, ANO7 for Erysipelotrichaceae (PIP = 0.449) in sigmoid colon. Functional analyses detected 94 significant GO terms and 11 pathways for various taxa in total, such as GO_NUCLEOSIDE_DIPHOSPHATASE_ACTIVITY for Butyrivibrio (FDR P = 1.30 × 10–4), KEGG_RENIN_ANGIOTENSIN_SYSTEM for Anaerostipes (FDR P = 3.16 × 10–2). Literature search results showed 12 genes prioritized by TWAS were associated with 12 diseases. For instance, SFTPD for an unclassified genus of Proteobacteria was related to atherosclerosis, and FUT2 for Bifidobacterium was associated with Crohn’s disease. Conclusions Our study results provided novel insights for understanding the genetic mechanism of gut microbiota, and attempted to provide clues for revealing the influence of genetic factors on gut microbiota for the occurrence and development of diseases.

scholarly journals A transcriptome-wide association study identifies susceptibility genes for Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shi Yao ◽  
Xi Zhang ◽  
Shu-Cheng Zou ◽  
Yong Zhu ◽  
Bo Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Nucleotide Polymorphisms ◽  
New Genes ◽  
Causal Genes ◽  
Regulated Gene Expression ◽  
Brain Tissues

AbstractGenome-wide association study (GWAS) has seen great strides in revealing initial insights into the genetic architecture of Parkinson’s disease (PD). Since GWAS signals often reside in non-coding regions, relatively few of the associations have implicated specific biological mechanisms. Here, we aimed to integrate the GWAS results with large-scale expression quantitative trait loci (eQTL) in 13 brain tissues to identify candidate causal genes for PD. We conducted a transcriptome-wide association study (TWAS) for PD using the summary statistics of over 480,000 individuals from the most recent PD GWAS. We identified 18 genes significantly associated with PD after Bonferroni corrections. The most significant gene, LRRC37A2, was associated with PD in all 13 brain tissues, such as in the hypothalamus (P = 6.12 × 10−22) and nucleus accumbens basal ganglia (P = 5.62 × 10−21). We also identified eight conditionally independent genes, including four new genes at known PD loci: CD38, LRRC37A2, RNF40, and ZSWIM7. Through conditional analyses, we demonstrated that several of the GWAS significant signals on PD could be driven by genetically regulated gene expression. The most significant TWAS gene LRRC37A2 accounts for 0.855 of the GWAS signal at its loci, and ZSWIM7 accounts for all the GWAS signals at its loci. We further identified several phenotypes previously associated with PD by querying the single nucleotide polymorphisms (SNPs) in the final model of the identified genes in phenome databases. In conclusion, we prioritized genes that are likely to affect PD by using a TWAS approach and identified phenotypes associated with PD.

O2-02-05: Novel candidate genes for late-onset Alzheimer's disease from a large scale association study of 20K functional variants

2006 ◽  
Vol 2 ◽  
pp. S33-S33
Author(s):  
Andrew Grupe ◽  
Yonghong Li ◽  
Charles Rowland ◽  
Richard Abraham ◽  
Paul Hollingworth ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Study ◽  
Candidate Genes ◽  
Large Scale ◽  
Late Onset ◽  
Functional Variants

scholarly journals Integration of genetically regulated gene expression and pharmacological library provides therapeutic drug candidates

2021 ◽  
Author(s):  
Takahiro Konuma ◽  
Kotaro Ogawa ◽  
Yukinori Okada
Keyword(s):  
Gene Expression ◽  
Drug Development ◽  
Association Study ◽  
Large Scale ◽  
Genome Wide Association Study ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Therapeutic Drug ◽  
Summary Statistics ◽  
Regulated Gene Expression

Abstract Approaches toward new therapeutics using disease genomics, such as genome-wide association study (GWAS), are anticipated. Here, we developed Trans-Phar [integration of transcriptome-wide association study (TWAS) and pharmacological database], achieving in silico screening of compounds from a large-scale pharmacological database (L1000 Connectivity Map), which have inverse expression profiles compared with tissue-specific genetically regulated gene expression. Firstly we confirmed the statistical robustness by the application of the null GWAS data and enrichment in the true-positive drug–disease relationships by the application of UK-Biobank GWAS summary statistics in broad disease categories, then we applied the GWAS summary statistics of large-scale European meta-analysis (17 traits; naverage = 201 849) and the hospitalized COVID-19 (n = 900 687), which has urgent need for drug development. We detected potential therapeutic compounds as well as anisomycin in schizophrenia (false discovery rate (FDR)-q = 0.056) and verapamil in hospitalized COVID-19 (FDR-q = 0.068) as top-associated compounds. This approach could be effective in disease genomics-driven drug development.

scholarly journals Galaxy spin direction distribution in HST and SDSS show similar large-scale asymmetry

2020 ◽  
Vol 37 ◽  
Author(s):  
Lior Shamir
Keyword(s):  
Large Scale ◽  
Spiral Galaxies ◽  
Hubble Space Telescope ◽  
Gravitational Interaction ◽  
Large Data ◽  
Sloan Digital Sky Survey ◽  
Data Sets ◽  
Dipole Axis ◽  
Data Set ◽  
The Asymmetry

Abstract Several recent observations using large data sets of galaxies showed non-random distribution of the spin directions of spiral galaxies, even when the galaxies are too far from each other to have gravitational interaction. Here, a data set of $\sim8.7\cdot10^3$ spiral galaxies imaged by Hubble Space Telescope (HST) is used to test and profile a possible asymmetry between galaxy spin directions. The asymmetry between galaxies with opposite spin directions is compared to the asymmetry of galaxies from the Sloan Digital Sky Survey. The two data sets contain different galaxies at different redshift ranges, and each data set was annotated using a different annotation method. The results show that both data sets show a similar asymmetry in the COSMOS field, which is covered by both telescopes. Fitting the asymmetry of the galaxies to cosine dependence shows a dipole axis with probabilities of $\sim2.8\sigma$ and $\sim7.38\sigma$ in HST and SDSS, respectively. The most likely dipole axis identified in the HST galaxies is at $(\alpha=78^{\rm o},\delta=47^{\rm o})$ and is well within the $1\sigma$ error range compared to the location of the most likely dipole axis in the SDSS galaxies with $z>0.15$ , identified at $(\alpha=71^{\rm o},\delta=61^{\rm o})$ .

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