Improving polygenic prediction from summary data by learning patterns of effect sharing across multiple phenotypes.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 10, 2024

Polygenic prediction of complex trait phenotypes has become important in human genetics, especially the context precision medicine. Recently, Morgante

Language: Английский

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Quantifying portable genetic effects and improving cross-ancestry genetic prediction with GWAS summary statistics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 29, 2022

Abstract Polygenic risk scores (PRS) calculated from genome-wide association studies (GWAS) of Europeans are known to have substantially reduced predictive accuracy in non-European populations, limiting its clinical utility and raising concerns about health disparities across ancestral populations. Here, we introduce a novel statistical framework named X-Wing improve performance ancestrally diverse quantifies local genetic correlations for complex traits between employs annotation-dependent estimation procedure amplify correlated effects combines multiple population-specific PRS into unified score with GWAS summary statistics alone as input. Through extensive benchmarking, demonstrate that pinpoints portable improves showing 18.7%-122.1% gain R 2 compared state-of-the-art methods based on statistics. Overall, addresses critical limitations existing approaches may broad applications cross-population polygenic prediction.

Language: Английский

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Optimizing and benchmarking polygenic risk scores with GWAS summary statistics

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 27, 2022

Background Polygenic risk score (PRS) is a major research topic in human genetics. However, significant gap exists between PRS methodology and applications practice due to often unavailable individual-level data for various tasks including model fine-tuning, benchmarking, ensemble learning. Results We introduce an innovative statistical framework optimize benchmark models using summary statistics of genome-wide association studies. This builds upon our previous work can fine-tune virtually all existing while accounting linkage disequilibrium. In addition, we provide learning strategy named PUMAS-ensemble combine multiple into without requiring external fitting. Through extensive simulations analysis many complex traits the UK Biobank, demonstrate that this approach closely approximates gold-standard analytical strategies based on validation, substantially outperforms state-of-the-art methods. Conclusions Our method powerful general modeling technique continue best-performing methods out there through could become integral component future applications.

Language: Английский

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Genome-Wide Association Study Using Genotyping by Sequencing for Bacterial Leaf Blight Resistance Loci in Local Thai Indica Rice

Agronomy, Journal Year: 2023, Volume and Issue: 13(5), P. 1286 - 1286

Published: April 29, 2023

Bacterial leaf blight (BLB) is a devastating disease caused by Xanthomonas oryzae pv. (Xoo), which poses significant threat to global rice production. In this study, genome-wide association study (GWAS) was conducted using the genotyping-by-sequencing (GBS) approach identify candidate single nucleotide polymorphisms (SNPs) associated with BLB resistance genes. The utilized 200 indica accessions inoculated seven distinct Xoo isolates and filtered highly SNPs minor allele frequency (MAF) of >5% call rate 75%. Four statistical models were used explore potential resistance, resulting in identification 32 on chromosomes 1–8 12 genome. Additionally, 179 genes located within ±100 kb SNP region, 49 selected as based their known functions plant defense mechanisms. Several identified, including two same linkage disequilibrium (LD) decay well-known gene (Xa1). These findings represent valuable resource for conducting further functional studies developing novel breeding strategies enhance crop’s disease.

Language: Английский

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Evaluating Genomic Polygenic Risk Scores for Childhood Acute Lymphoblastic Leukemia in Latinos

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: June 12, 2023

The utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type cancer in children. Previous PRS ALL were based on significant loci observed genome-wide association studies (GWAS), even though genomic have shown to improve prediction performance a number complex diseases. In United States, Latino (LAT) children highest ALL, but transferability LAT studied. this study we constructed and either non-Latino white (NLW) GWAS or multi-ancestry GWAS. We found that best performed similarly between held-out NLW samples (PseudoR

Language: Английский

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