Gil McVean

Preventing premature deaths through polygenic risk scores

This study evaluates how polygenic risk scores can optimize screening programs to reduce premature deaths by tailoring screening ages based on genetic risk.

Exposure accumulation drives age-dependent disease architectures and polygenic risk scores

The paper shows that environmental variance increases with age, reducing heritability and PRS accuracy for multiple traits and diseases, suggesting younger cohorts are better for risk prediction models.

UK Biobank release and systematic evaluation of optimised polygenic risk scores for 53 diseases and quantitative traits

The paper releases and evaluates polygenic risk scores for 53 diseases and traits in the UK Biobank and shows they outperform existing scores.

Optimal strategies for learning multi-ancestry polygenic scores vary across traits

This study shows that optimal polygenic score strategies vary by trait and ancestry, with smaller African-ancestry training sets outperforming larger European-ancestry sets for some traits.

Topic modelling with ICD10-informed priors identifies novel genetic loci associated with multimorbidities in UK Biobank

The paper develops treeLFA, a topic modeling method using ICD10 priors to identify multimorbidity clusters in UK Biobank, and finds genetic loci associated with these clusters.

Age-dependent topic modelling of comorbidities in UK Biobank identifies disease subtypes with differential genetic risk

This paper introduces an age-dependent topic modelling method to identify disease subtypes with differential genetic risk using UK Biobank and All of Us data.

A unified genealogy of modern and ancient genomes

This paper introduces a non-parametric method to infer human genealogical history from modern and ancient genomes, demonstrating its ability to reconstruct relationships and identify descendants of ancient samples.

The impact of age on genetic risk for common diseases

This paper investigates how genetic risk for common diseases changes with age using UK Biobank data, finding that most genetic risk factors have a decreasing impact over time.

Elucidating relationships between P.falciparum prevalence and measures of genetic diversity with a combined genetic-epidemiological model of malaria

This paper develops a combined genetic-epidemiological model to explore relationships between Plasmodium falciparum prevalence and genetic diversity, finding that mixed infection statistics respond quickly to prevalence changes.

Detection of simple and complex de novo mutations without, with, or with multiple reference sequences

The paper introduces Corticall, a graph-based method to detect de novo mutations using short-read and long-read data, validated on Plasmodium falciparum crosses.

Dating genomic variants and shared ancestry in population-scale sequencing data

The paper estimates the age of over 45 million SNPs in the human genome and uses this to infer shared ancestry and evolutionary history.

New insights into malaria susceptibility from the genomes of 17,000 individuals from Africa, Asia, and Oceania

This study identifies five genome-wide associations with severe malaria risk in 17,000 individuals from Africa, Asia, and Oceania, including a new variant linked to cerebral malaria.

Mapping the drivers of within-host pathogen evolution using massive data sets

The paper develops a Bayesian method to detect host influences on pathogen evolution using large datasets, demonstrating improved precision in identifying HLA-induced selection in HIV-1.

HLA*PRG:LA - HLA typing from linearly projected graph alignments

HLA*PRG:LA is a graph alignment model for HLA typing that achieves high accuracy across various sequencing data types.

Bayesian meta-analysis across genome-wide association studies of diverse phenotypes

This paper introduces a Bayesian framework for meta-analyzing GWAS across diverse phenotypes, showing increased power compared to frequentist methods.

Real-time search of all bacterial and viral genomic data

The paper introduces a DNA search engine for microbial genomic data that enables real-time search and analysis of bacterial and viral sequences.

Selfish mutations dysregulating RAS-MAPK signaling are pervasive in aged human testes

The paper identifies 61 novel mutations in the aged human testes, most affecting the RAS-MAPK pathway, showing evidence of selfish selection in the male germline.

Systematic classification of shared components of genetic risk for common human diseases

This study systematically classifies shared genetic risk components across common human diseases using UK Biobank data, revealing molecular connectivity with clinical implications.

Integrating long-range connectivity information into de Bruijn graphs

The paper introduces a new data structure called the Linked de Bruijn Graph (LdBG) that integrates long-range connectivity information into de Bruijn graphs, improving performance in genome assembly and variant calling.

Deconvolution of multiple infections in Plasmodium falciparum from high throughput sequencing data

The paper develops a statistical method to deconvolve multiple Plasmodium falciparum strains from sequencing data, enabling detailed analysis of mixed infections.

Bayesian analysis of genetic association across tree-structured routine healthcare data in the UK Biobank

This paper develops a Bayesian framework to analyze genetic associations with healthcare phenotypes in the UK Biobank, identifying over 2,000 diagnostic term associations and novel immune-mediated disease links.

Genome-wide genetic data on ~500,000 UK Biobank participants

Quality-controlled genotypes for 488,377 UK Biobank participants at 805,426 markers, imputed to ~96 million variants, plus ancestry PCs, kinship (30.3% have close relatives enrolled) and HLA calls.

Genome Graphs

This paper introduces genome graphs as an alternative to linear reference genomes, showing they improve read mapping and variant calling compared to the standard GRCh38 reference.

Practical Use of Methods for Imputation of HLA Alleles from SNP Genotype Data

The paper evaluates HLA imputation methods using a multi-ethnic panel, introduces a new method HLA*IMP:03, and shows it achieves high accuracy without requiring probability thresholds.

A reference dataset of 5.4 million phased human variants validated by genetic inheritance from sequencing a three-generation 17-member pedigree

The paper generates a high-confidence variant catalogue from whole-genome sequencing of a three-generation pedigree, validated by haplotype transmission and showing improved accuracy over existing benchmarks.

Efficient coalescent simulation and genealogical analysis for large sample sizes

The paper introduces efficient methods for coalescent simulation and genealogical analysis that scale to large sample sizes and improve speed and storage efficiency.

High-accuracy HLA type inference from whole-genome sequencing data

This paper develops HLA*PRG, a method for high-accuracy HLA type inference from whole-genome sequencing data, achieving accuracy comparable to gold-standard methods.

Genome variation and meiotic recombination in Plasmodium falciparum: insights from deep sequencing of genetic crosses

The paper uses deep sequencing of genetic crosses in Plasmodium falciparum to analyze genome variation and meiotic recombination, revealing INDELs as dominant polymorphisms and providing insights into recombination patterns and drug resistance mechanisms.

Rapid antibiotic resistance predictions from genome sequence data for S. aureus and M. tuberculosis.

This paper develops a tool to predict antibiotic resistance in S. aureus and M. tuberculosis from genome sequences with high accuracy and speed.

Stable recombination hotspots in birds

The paper identifies recombination hotspots in two bird species, finding they are shared between species and enriched near CpG islands and transcription start sites.