Cited by Addressing Cardiovascular Toxicity Risk of Electronic Nicotine Delivery Systems in the Twenty-First Century: “What Are the Tools Needed for the Job?” and “Do We Have Them?”

Transcriptome-wide association studies: recent advances in methods, applications and available databases DOI

Jialin Mai, Mingming Lu,

Qianwen Gao

et al.

Communications Biology, Journal Year: 2023, Volume and Issue: 6(1)

Published: Sept. 1, 2023

Abstract Genome-wide association study has identified fruitful variants impacting heritable traits. Nevertheless, identifying critical genes underlying those significant been a great task. Transcriptome-wide (TWAS) is an instrumental post-analysis to detect gene-trait associations focusing on modeling transcription-level regulations, which made numerous progresses in recent years. Leveraging from expression quantitative loci (eQTL) regulation information, TWAS advantages detecting functioning regulated by disease-associated variants, thus providing insight into mechanisms of diseases and other phenotypes. Considering its vast potential, this review article comprehensively summarizes TWAS, including the methodology, applications available resources.

Language: Английский

Citations

Genetic and molecular architecture of complex traits DOI

Tuuli Lappalainen, Yang Li, Sohini Ramachandran

et al.

Cell, Journal Year: 2024, Volume and Issue: 187(5), P. 1059 - 1075

Published: Feb. 1, 2024

Language: Английский

Citations

Multi-ancestry meta-analysis of tobacco use disorder identifies 461 potential risk genes and reveals associations with multiple health outcomes DOI

Sylvanus Toikumo,

Mariela Jennings,

Benjamin K. Pham

et al.

Nature Human Behaviour, Journal Year: 2024, Volume and Issue: 8(6), P. 1177 - 1193

Published: April 17, 2024

Language: Английский

Citations

Multi-ancestry and multi-trait genome-wide association meta-analyses inform clinical risk prediction for systemic lupus erythematosus DOI

Chachrit Khunsriraksakul,

Qinmengge Li,

Havell Markus

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Feb. 7, 2023

Systemic lupus erythematosus is a heritable autoimmune disease that predominantly affects young women. To improve our understanding of genetic etiology, we conduct multi-ancestry and multi-trait meta-analysis genome-wide association studies, encompassing 12 systemic cohorts from 3 different ancestries 10 genetically correlated diseases, identify 16 novel loci. We also perform transcriptome-wide computational drug repurposing analysis, cell type enrichment analysis. discover putative classes, including histone deacetylase inhibitor could be repurposed to treat lupus. multiple types enriched with target genes, such as non-classical monocytes B cells, which may targeted for future therapeutics. Using this newly assembled result, further construct polygenic risk score models demonstrate integrating clinical lab biomarkers improves the diagnostic accuracy using Vanderbilt BioVU Michigan Genomics Initiative biobanks.

Language: Английский

Citations

The landscape of the methodology in drug repurposing using human genomic data: a systematic review DOI

Lijuan Wang, Ying Lü, Doudou Li

et al.

Briefings in Bioinformatics, Journal Year: 2024, Volume and Issue: 25(2)

Published: Jan. 22, 2024

Abstract The process of drug development is expensive and time-consuming. In contrast, repurposing can be introduced to clinical practice more quickly at a reduced cost. Over the last decade, there has been significant expansion large biobanks that link genomic data electronic health record data, public availability various databases containing biological information rapid novel methodologies algorithms in integrating different sources data. This review aims provide thorough summary strategies utilize seek drug-repositioning opportunities. We searched MEDLINE EMBASE identify eligible studies up until 1 May 2023, with total 102 finally included after two-step parallel screening. summarized commonly used for repurposing, including Mendelian randomization, multi-omic-based network-based illustrated each strategy examples, as well implemented. By leveraging existing knowledge infrastructure expedite discovery reduce costs, potentially identifies new therapeutic uses approved drugs efficient targeted manner. However, technical challenges when types biased or incomplete understanding interactions are important hindrances cannot disregarded pursuit identifying applications. offers an overview methodologies, providing valuable insights guiding future directions advancing studies.

Language: Английский

Citations

Genetic imputation of kidney transcriptome, proteome and multi-omics illuminates new blood pressure and hypertension targets DOI

Xiaoguang Xu, Chachrit Khunsriraksakul, James Eales

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 19, 2024

Abstract Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated validated gene expression prediction models for the purpose transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP which 399 were prioritised as contributors to regulation. Imputation proteome microRNAome uncovered 97 renal proteins 11 miRNAs BP. Integration plasma proteomics metabolomics illuminated circulating levels myo-inositol, 4-guanidinobutanoate angiotensinogen downstream effectors several ( SLC5A11 , AGMAT AGT respectively). showed that genetically determined reduction may mimic effects rare loss-of-function variants on mRNA/protein lead an increase (e.g., ENPEP ). demonstrated a strong correlation (r = 0.81) protein-coding between cells harvested from urine highlighting diagnostic potential urinary cell transcriptomics. adenylyl cyclase activators repurposing opportunity hypertension illustrated examples BP-elevating anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our provide new biological insights into genetic drive clinical translation hypertension.

Language: Английский

Citations

A multi-tissue, splicing-based joint transcriptome-wide association study identifies susceptibility genes for breast cancer DOI

Guimin Gao,

Julian McClellan,

Alvaro Barbeira

et al.

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: 111(6), P. 1100 - 1113

Published: May 10, 2024

Language: Английский

Citations

Integrating single cell expression quantitative trait loci summary statistics to understand complex trait risk genes DOI

Lida Wang, Chachrit Khunsriraksakul, Havell Markus

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 20, 2024

Transcriptome-wide association study (TWAS) is a popular approach to dissect the functional consequence of disease associated non-coding variants. Most existing TWAS use bulk tissues and may not have resolution reveal cell-type specific target genes. Single-cell expression quantitative trait loci (sc-eQTL) datasets are emerging. The largest bulk- sc-eQTL most conveniently available as summary statistics, but been broadly utilized in TWAS. Here, we present new method EXPRESSO (EXpression PREdiction with Summary Statistics Only), analyze which also integrates 3D genomic data epigenomic annotation prioritize causal substantially improves methods. We apply multi-ancestry GWAS for 14 autoimmune diseases. uniquely identifies 958 novel gene x associations, 26% more than second-best method. Among them, 492 unique cell type level analysis missed by using whole blood. develop aware drug repurposing pipeline, leverages results identify compounds that can reverse expressions relevant types. Our point multiple drugs therapeutic potentials, including metformin 1 diabetes, vitamin K ulcerative colitis.

Language: Английский

Citations

Smoking-related dysregulation of plasma circulating microRNAs: the Rotterdam study DOI

Irma Karabegović, Silvana C. E. Maas,

Yu Shuai

et al.

Human Genomics, Journal Year: 2023, Volume and Issue: 17(1)

Published: July 10, 2023

Abstract Background MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression. Differential miRNA expression, which is widely shown to be associated with the pathogenesis various diseases, can influenced by lifestyle factors, including smoking. This study aimed investigate plasma signature smoking habits, potential effect cessation on levels, and relate findings lung cancer incidence. Results A targeted RNA-sequencing approach measured levels in 2686 participants from population-based Rotterdam cohort. The association between cigarette (current versus never) 591 well-expressed miRNAs was assessed via adjusted linear regression models, identifying 41 smoking-associated that passed Bonferroni-corrected threshold ( P < 0.05/591 = 8.46 × 10 –5 ). Moreover, we found 42 a significant ) current (reference group) former smokers. Then, used models explore time expression levels. two were significantly different within 5 years 0.05/41 1.22 –3 smokers, while for 15 19 finally, 38 after more than These results imply reversibility at least out smoking-miRNAs following cessation. Next, 8 smoking-related nominally 0.05) incidence cancer. Conclusions demonstrates dysregulation miRNAs, might have when comparing groups. identified involved several cancer-related pathways include Our may lay groundwork further investigation as mechanism linking smoking,

Language: Английский

Citations

NCH-DDA: Neighborhood contrastive learning heterogeneous network for drug–disease association prediction DOI

Peiliang Zhang, Chao Che, Bo Jin

et al.

Expert Systems with Applications, Journal Year: 2023, Volume and Issue: 238, P. 121855 - 121855

Published: Sept. 29, 2023

Language: Английский

Citations