polygenic risk

BLocPRS: locus-aware ensembles of polygenic scores provide accurate linear prediction

BLocPRS improves polygenic risk score prediction by combining locus-specific weights from different PRSs, achieving higher accuracy in UK Biobank and extending to non-European populations.

Genetics in Context: Social Factors Modify Polygenic Risk Across Multiple Cardiometabolic Diseases

The paper examines how social determinants of health modify polygenic risk scores for cardiometabolic diseases and shows that integrating social and genetic factors improves disease prediction.

A family-aware All of Us benchmark for polygenic prediction and genomic machine learning

The paper introduces a family-aware benchmark for polygenic prediction using All of Us data, enabling comparison of PRS and machine learning models across 14 traits with strong predictive performance.

A Polygenic Score for Smoking Persistence Captures Differences in Cessation Age

This paper develops a polygenic score for smoking persistence and finds it is associated with earlier or later cessation ages across diverse populations.

Genome-wide LD scores enable robust heritability and genetic correlation estimation from summary statistics across genetic ancestries

SUMMIT improves heritability and genetic correlation estimation across diverse ancestries using LD scores and GWAS summary statistics, showing better accuracy in non-European populations.

Functional architecture of rare protein coding variation across 786,871 exomes

The paper introduces KASM to integrate functional annotations and estimate heritability of rare protein coding variants across 786,871 exomes, finding higher heritability than previous estimates.

S4-Oligo: optimizing polygenic score methods for clinical deployment

This paper introduces S4-Oligo, an optimized polygenic score method for clinical use, which matches or exceeds existing models' accuracy while using fewer SNPs.

Accounting for gene action improves the accuracy of polygenic scores for some complex traits

This study introduces PGSa,d, a polygenic scoring framework that incorporates both additive and dominance effects, showing improved accuracy for traits with significant dominance contributions.

Sequence-based variant-effect predictions reveal trait-specific regulatory-layer profiles of complex-trait heritability

The paper uses sequence-based variant-effect predictions to show that different regulatory layers contribute variably to the heritability of complex traits within tissues.

Triangulating evidence to detect signatures of stabilizing selection acting on protein levels in humans

The paper detects stabilizing selection on human plasma proteins by integrating genetic and fitness-related evidence across multiple approaches.

Melanoma germline genetics: immune, cancer driver, and Wnt signaling genes

This paper identifies 116 risk loci for melanoma through GWAS, links susceptibility to immunity and Wnt signaling, and develops a PRS improving risk prediction.

The landscape of polygenic score prediction accuracy and transportability across the phenome in ancestrally diverse populations

This study evaluates polygenic score prediction accuracy and cross-ancestry portability across 3,994 PGSs in diverse populations, identifying factors affecting their performance and equity.

Significance filtering induces denominator selection bias in local genetic correlation: closed-form characterisation, a gate-aware correction, and an applicability diagnostic

The paper identifies a bias in local genetic correlation estimation due to significance filtering and proposes a correction method with a diagnostic tool.

Clinical history shapes the predictive value of polygenic risk

The paper develops and validates polygenic risk scores (PRS) for 150 diseases and mortality using UK Biobank and FinnGen data, showing genetic information provides the largest predictive gains for certain diseases but not others.

A Genome-wide Genetic Data Resource for the 45 and Up Study

The paper generates and validates genome-wide genetic data for the 45 and Up Study cohort, enhancing its utility for disease risk and precision health research.

Structural variants contribute substantially to complex trait heritability

The paper quantifies the contribution of structural variants to complex trait heritability using MiXeRSV, finding SVs explain up to 32% of heritability in some traits.

GeneSIS: enhancing transferability of polygenic scores with variant-level gene-by-sex interaction effects

GeneSIS improves polygenic score transferability by incorporating gene-by-sex interactions, enhancing prediction accuracy in non-European populations for 32 traits.

SPLENDID incorporates continuous genetic ancestry in biobank-scale data to improve polygenic risk prediction across diverse populations

SPLENDID improves polygenic risk prediction across diverse populations by incorporating continuous genetic ancestry without requiring discrete ancestry labels.

Estrogen interactions with breast cancer risk variants in regulatory DNA

The paper identifies estrogen-modulated SNVs associated with breast cancer risk and shows their interaction with reproductive factors using polygenic risk scores.

Multi-trait Polygenic Profiling and Survival Free of Dementia and Disability: Results from the Health and Retirement Study

This study shows that adverse polygenic profiles for dementia are linked to higher risks of dementia, disability, or death in middle-aged and older adults.

Rare extreme polygenic risk scores strongly indicate Alzheimer's disease risk

The paper identifies individuals with extreme polygenic risk scores (PRS) for Alzheimer's disease (AD) and shows they have significantly elevated AD risk across multiple ancestries and APOE diplotypes.

Alzheimer's Polygenic Risk Scores Are Not Interchangeable: Evidence from 1,752 Models

The paper evaluates 1,752 polygenic risk score models for Alzheimer's disease and finds significant variability in results across methods and ancestries.

Molecular Underpinnings of Retinal Traits Shared with Major Psychiatric Disorders

The paper identifies shared genetic variants between major psychiatric disorders and retinal traits, revealing molecular mechanisms linking retinal morphology to neurodevelopmental and neurotransmission processes.

Hypertrophic cardiomyopathy: a genome wide association meta-analysis and polygenic risk score

This paper identifies novel genetic loci for hypertrophic cardiomyopathy through GWAS and develops a polygenic risk score associated with HCM diagnosis and outcomes.

Genetic Architecture and Sample Size Impact Relative Performance of Nonlinear Machine Learning and Standard Polygenic Risk Scores

This study evaluates when nonlinear machine learning methods outperform standard polygenic risk scores, finding their effectiveness depends on genetic architecture and sample size.

Genetic architectures of brain-related traits are shaped by strong selective constraints

The paper compares genetic architectures of brain-related traits and finds they have weaker associations and stronger selection pressures compared to other traits.

Mitochondrial DNA copy number in neurodegenerative diseases: a global meta-analysis of 156 comparisons across 76 studies

This study meta-analyzes 156 comparisons across 76 studies to assess mtDNA copy number changes in neurodegenerative diseases, finding no overall difference but significant heterogeneity.

A Principled Framework for Using Correlated Traits to Improve Risk Prediction

This paper develops a framework to improve polygenic risk scores by using correlated traits, showing that helper traits can significantly enhance prediction accuracy for type 2 diabetes.

Locus-specific gene-context interactions improve polygenic prediction

This paper introduces PGSC, a polygenic score framework that incorporates locus-specific gene-context interactions, showing improved prediction across multiple traits and ancestries.

From Data Curation to Risk Reporting: A Pipeline for Polygenic Risk Scores

This paper presents a pipeline for polygenic risk score calculation that includes data curation, statistical methods, and reporting, resulting in a curated database and interpretable reports for PRS analysis.