Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer DOI Creative Commons
Congcong Chen, Yang Li, Yayun Gu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal and improve disease risk prediction. Here, we applied massively parallel reporter assays perform NSCLC variant-to-function mapping at scale. A total 1249 candidate were evaluated, 30 potential within 12 loci identified. Accordingly, proposed three architectures underlying susceptibility: multiple in a single haplotype block (e.g. 4q22.1), blocks 5p15.33), variant 20q11.23). We developed modified polygenic score using from Chinese populations, improving performance prediction 450,821 Europeans UK Biobank. Our findings not only augment understanding architecture susceptibility but also provide strategy advance stratification. Determining GWAS crucial for mechanisms. authors apply MPRA (NSCLC) scale propose distinct susceptibility.

Language: Английский

Early risk identification and prevention of bipolar disorder: ethical considerations and user perspectives DOI
Rudolf Uher, Alyson Zwicker

Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Transferability of Single‐ and Cross‐Tissue Transcriptome Imputation Models Across Ancestry Groups DOI Creative Commons

Inti Pagnuco,

Stephen Eyre, Magnus Rattray

et al.

Genetic Epidemiology, Journal Year: 2025, Volume and Issue: 49(1)

Published: Jan. 1, 2025

ABSTRACT Transcriptome‐wide association studies (TWAS) investigate the links between genetically regulated gene expression and complex traits. TWAS involves imputing using quantitative trait loci (eQTL) as predictors testing imputed trait. The effectiveness of depends on accuracy these imputation models, which require genotype data from same samples. However, publicly accessible resources, such Genotype Tissue Expression (GTEx) Project, are biased toward individuals European ancestry, potentially reducing prediction into other ancestry groups. This study explored eQTL transferability across groups by comparing two models: PrediXcan (tissue‐specific) UTMOST (cross‐tissue). Both models were trained tissues GTEx Project then tested sets African American individuals. Results showed that both performed best when training group, with cross‐tissue approach generally outperforming tissue‐specific approach. underscores detection is influenced tissue context. Developing ancestry‐specific reference panels can improve accuracy, enhancing analysis our understanding biological processes contributing to

Language: Английский

Citations

0
The clinical value and most informative threshold of polygenic risk score in the Quebec City Case-Control Asthma Cohort DOI Creative Commons
Martin Pariès, Stéphanie Bougeard,

Aïda Eslami

et al.

BMC Pulmonary Medicine, Journal Year: 2025, Volume and Issue: 25(1)

Published: Jan. 15, 2025

Language: Английский

Citations

0
Variational Autoencoder-based Model Improves Polygenic Prediction in Blood Cell Traits DOI Creative Commons
Xiaoqi Li, Minxing Pang,

Jia Wen

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 18, 2025

Abstract Genetic prediction of complex traits, enabled by large-scale genomic studies, has created new measures to understand individual genetic predisposition. Polygenic Risk Scores (PRS) offer a way aggregate information across the genome, enabling personalized risk for traits and diseases. However, conventional PRS calculation methods that rely on linear models are limited in their ability capture patterns interaction effects high-dimensional data. In this study, we seek improve predictive power through applying advanced deep learning techniques. We show Variational AutoEncoder-based model construction (VAE-PRS) outperforms currently state-of-the-art biobank-level data 14 out 16 blood cell while being computationally efficient. Through comprehensive experiments, found VAE-PRS offers shows robust performance different pre-screened variant sets. Furthermore, is easily interpretable via assessing contribution each marker final score SHapley Additive exPlanations (SHAP) method, providing potential insights identifying trait-associated variants. summary, presents novel measure harnessing methods, which could further facilitate development medicine research.

Language: Английский

Citations

0
Massively parallel variant-to-function mapping determines functional regulatory variants of non-small cell lung cancer DOI Creative Commons
Congcong Chen, Yang Li, Yayun Gu

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Genome-wide association studies have identified thousands of genetic variants associated with non-small cell lung cancer (NSCLC), however, it is still challenging to determine the causal and improve disease risk prediction. Here, we applied massively parallel reporter assays perform NSCLC variant-to-function mapping at scale. A total 1249 candidate were evaluated, 30 potential within 12 loci identified. Accordingly, proposed three architectures underlying susceptibility: multiple in a single haplotype block (e.g. 4q22.1), blocks 5p15.33), variant 20q11.23). We developed modified polygenic score using from Chinese populations, improving performance prediction 450,821 Europeans UK Biobank. Our findings not only augment understanding architecture susceptibility but also provide strategy advance stratification. Determining GWAS crucial for mechanisms. authors apply MPRA (NSCLC) scale propose distinct susceptibility.

Language: Английский

Citations

0