Enhancing portability of trans-ancestral polygenic risk scores through tissue-specific functional genomic data integration DOI Creative Commons
Bradley Crone, Alan P. Boyle

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(8), P. e1011356 - e1011356

Published: Aug. 7, 2024

Portability of trans-ancestral polygenic risk scores is often confounded by differences in linkage disequilibrium and genetic architecture between ancestries. Recent literature has shown that prioritizing GWAS SNPs with functional genomic evidence over strong association signals can improve model portability. We leveraged three RegulomeDB-derived regulatory annotations—SURF, TURF, TLand—to construct models across a set quantitative binary traits highlighting mutations tagged trait-associated tissue annotations. Tissue-specific prioritization TURF TLand provide significant improvement accuracy standard score (PRS) all traits. developed the Trans-ancestral Iterative Tissue Refinement (TITR) algorithm to PRS prioritize multiple trait-implicated tissues. TITR-constructed show increased predictive single prioritization. This indicates our TITR approach captures more comprehensive view systems implicated tissues contribute variance trait expression.

Language: Английский

Advancements and applications of single-cell multi-omics techniques in cancer research: Unveiling heterogeneity and paving the way for precision therapeutics DOI Creative Commons

Anqi Liang,

Ying Kong, Zhi Hong Chen

et al.

Biochemistry and Biophysics Reports, Journal Year: 2023, Volume and Issue: 37, P. 101589 - 101589

Published: Nov. 29, 2023

Single-cell multi-omics technologies have revolutionized cancer research by allowing us to examine individual cells at a molecular level. Unlike traditional bulk omics approaches, which analyze populations of together, single-cell enables uncover the heterogeneity within tumors and understand unique characteristics different cell populations. By doing so, we can identify rare subpopulations that are influential in tumor growth, metastasis, resistance therapy. Moreover, analysis provides valuable insights into immune response triggered various therapeutic interventions, such as checkpoint blockade, chemotherapy, It also helps better intricate microenvironment its impact on patient prognosis treatment. This comprehensive review focuses recent advancements methodologies, with an emphasis technologies. highlights important role these techniques uncovering complexity tumorigenesis multiple applications research, well their equally great contributions other areas immunology. Through multi-omics, gain deeper understanding biology pave way for more precise effective strategies. Apart from those above, this paper aims introduce live imaging technology, latest developments protein detection techniques, explore seamless integration technology.

Language: Английский

Citations

24
Association between periodontitis and breast cancer: two-sample Mendelian randomization study DOI Creative Commons
Ming Ding, Zhonghua Zhang, Zhu Chen

et al.

Clinical Oral Investigations, Journal Year: 2023, Volume and Issue: 27(6), P. 2843 - 2849

Published: Feb. 7, 2023

The purpose of this study was to investigate whether there is a causal relationship between periodontitis and breast cancer by Mendelian randomization analysis.

Language: Английский

Citations

22
Genetic effects of sequence-conserved enhancer-like elements on human complex traits DOI Creative Commons
Xiang Zhu, Shining Ma, Wing Hung Wong

et al.

Genome biology, Journal Year: 2024, Volume and Issue: 25(1)

Published: Jan. 2, 2024

Abstract Background The vast majority of findings from human genome-wide association studies (GWAS) map to non-coding sequences, complicating their mechanistic interpretations and clinical translations. Non-coding sequences that are evolutionarily conserved biochemically active could offer clues the mechanisms underpinning GWAS discoveries. However, genetic effects such have not been systematically examined across a wide range tissues traits, hampering progress fully understand regulatory causes complex traits. Results Here we develop simple yet effective strategy identify functional elements exhibiting high levels human-mouse sequence conservation enhancer-like biochemical activity, which scales well 313 epigenomic datasets 106 cell types. Combined with 468 European (EUR) East Asian (EAS) ancestries, these show tissue-specific enrichments heritability causal variants for many significantly stronger than based on enhancers without conservation. These also help prioritize candidate genes functionally relevant body mass index (BMI) schizophrenia but were reported in previous large sample sizes. Conclusions Our provide comprehensive assessment how sequence-conserved affect traits diverse demonstrate generalizable integrating evolutionary data elucidate disease genetics.

Language: Английский

Citations

5
Association Between Whole Blood–Derived Mitochondrial DNA Copy Number, Low‐Density Lipoprotein Cholesterol, and Cardiovascular Disease Risk DOI Creative Commons
Xue Liu,

Xianbang Sun,

Yuankai Zhang

et al.

Journal of the American Heart Association, Journal Year: 2023, Volume and Issue: 12(20)

Published: Oct. 7, 2023

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods Results We performed cross-sectional prospective association analyses of blood-derived mtDNA CN outcomes in 27 316 participants 8 cohorts multiple racial ethnic groups with whole-genome sequencing. also Mendelian randomization to explore causal relationships coronary heart (CHD) cardiometabolic risk factors (obesity, diabetes, hypertension, hyperlipidemia).

Language: Английский

Citations

12
Recent advances in regulating lipid metabolism to prevent coronary heart disease DOI

Jingchun Du,

Wei Wu, Boran Zhu

et al.

Chemistry and Physics of Lipids, Journal Year: 2023, Volume and Issue: 255, P. 105325 - 105325

Published: July 4, 2023

Language: Английский

Citations

11
Looking back on 30+ years of the Johnston County Osteoarthritis Project while looking forward with the Johnston County Health Study: A narrative review DOI
Yvonne M. Golightly, Jordan B. Renner, Charles G. Helmick

et al.

Osteoarthritis and Cartilage, Journal Year: 2024, Volume and Issue: 32(4), P. 430 - 438

Published: Jan. 17, 2024

Language: Английский

Citations

4
Systematic elucidation of genetic mechanisms underlying cholesterol uptake DOI Creative Commons
Marisa C. Hamilton, James D. Fife, Ersin Akıncı

et al.

Cell Genomics, Journal Year: 2023, Volume and Issue: 3(5), P. 100304 - 100304

Published: April 21, 2023

Genetic variation contributes greatly to LDL cholesterol (LDL-C) levels and coronary artery disease risk. By combining analysis of rare coding variants from the UK Biobank genome-scale CRISPR-Cas9 knockout activation screening, we substantially improve identification genes whose disruption alters serum LDL-C levels. We identify 21 in which significantly alter at least partially through altered uptake. use co-essentiality-based gene module show that dysfunction RAB10 vesicle transport pathway leads hypercholesterolemia humans mice by impairing surface receptor Further, demonstrate loss function

Language: Английский

Citations

10
A bidirectional Mendelian randomization study integrating genome-wide association studies, expression quantitative trait locus, and methylation quantitative trait locus data revealed causal relationship between heavy cigarette dependence and Barrett’s esophagus DOI Creative Commons
An Zhou, Meichun Zeng,

Xian-Hua Wang

et al.

SAGE Open Medicine, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 1, 2025

Background: The association between smoking dependence and the risk of developing Barrett’s esophagus remains unclear. This study aimed to investigate whether a causal relationship exists esophagus, using Mendelian randomization analysis. Methods: Two-sample analysis was conducted evaluate impact esophagus. Additionally, we applied summary data-based techniques combine information from genome-wide studies (GWAS) with expression quantitative trait locus methylation locus. Results: Multivariable showed an per day (odds ratio = 1.2, 95% confidence interval: 1.038–1.38, p 0.014) or current 2.41, 1.06–5.5, 0.037) Inverse variance-weighted methods bidirectional also revealed that significantly associated elevated risks 1.34, 1.092–1.649, 0.005), while susceptibility factor for 1.05, 1.017–1.087, 0.003). By incorporating consistent associations DNA smoke/Barrett’s gene expression, identified genetic variant-cg00935895-RBM43 (ENSG00000184898)-smoke/Barrett’s axis exerted effect on by altering level, which regulated level RBM43. Conclusions: Our provides evidence perspective, sheds new light potential role RBM43 as mediator in facilitating

Language: Английский

Citations

0
Characterization of non-coding variants associated with transcription-factor binding through ATAC-seq-defined footprint QTLs in liver DOI
Max F. Dudek,

Brandon M. Wenz,

Christopher D. Brown

et al.

The American Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

Citations

0
Cardiovascular Disease Knowledge Portal: A Community Resource for Cardiovascular Disease Research DOI
Maria C. Costanzo, Carolina Roselli,

MacKenzie Brandes

et al.

Circulation Genomic and Precision Medicine, Journal Year: 2023, Volume and Issue: 16(6)

Published: Oct. 10, 2023

Language: Английский

Citations

9