Wenhan Lu

Large language model classifies prior evidence in gene-phenotype associations

PESTO classifies gene-phenotype associations as Novel, Hypothesized, Existing, or Established using a large language model and structured genetic evidence, identifying 7% as Novel and 21% as Hypothesized in 940 associations.

Effect heterogeneity reveals complex pleiotropic effects of rare coding variants

ALLSPICE identifies heterogeneous rare variant effects across traits in gene-trait associations using summary statistics from the UK Biobank.

Estimating the contribution of coding mutations to autism

The paper estimates the contribution of de novo coding mutations to autism using data from 38,680 trios, finding they explain 3.4% of autism variance.

Rare variation illuminates the distinct and pleiotropic genetic architecture of autism across neuropsychiatric traits

The paper identifies 253 autism-associated genes using rare variation from 62,429 individuals and finds pleiotropy across physiological systems and developmental disorders.

A unified framework for local-ancestry-aware genetic association analysis across biobanks

FELIX improves genetic association analysis by accounting for local ancestry in admixed populations, increasing significant loci and improving polygenic score prediction.

Rare Coding Variants Reveal Distinct Genetic Architectures Across Multidimensional Sleep Phenotypes

The paper identifies 260 genes associated with sleep phenotypes using rare coding variants from large-scale sequencing data, revealing distinct genetic architectures and biological mechanisms across different sleep measurements.

The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration

The paper establishes a global consortium to discover rare genetic associations by integrating data from multiple biobanks, identifying 514 gene-trait associations, many detectable only through cross-ancestry meta-analysis.

Systematic common and rare variant association testing in 392,030 whole genomes in All of Us

The paper performs large-scale GWAS and RVAS on 392,030 whole genomes from All of Us, identifying 49,863 associations and 193 novel pLoF gene-phenotype links through meta-analysis with UK Biobank.

Phenome-derived polygenic scores and social determinants jointly shape context-dependent disease risk

This paper constructs phenome-derived polygenic scores and evaluates how they, along with social determinants of health, influence disease risk across different populations and diseases.

Integrating 730,947 exome sequences with clinical literature improves gene discovery

gnomAD v4 (730,947 exomes) brings LOFTEE-2 loss-of-function annotation (0.90 precision, strict mode), missense-aware constraint, and LLM-mined literature evidence combined with constraint to rank disease genes.

Multi-trait and multi-ancestry genetic analysis of comorbid lung diseases and traits improves genetic discovery and polygenic risk prediction

This paper improves genetic discovery and polygenic risk prediction for respiratory diseases by analyzing multiple traits and ancestries, identifying novel loci and developing a new polygenic risk score method.

Mechanism of age-related accumulation of mitochondrial DNA mutations in human blood

The paper investigates the mechanism of age-related mtDNA mutation accumulation in human blood using whole genome sequences, revealing a two-step process involving cryptic mutations and clonal expansion.

Pan-UK Biobank GWAS improves discovery, analysis of genetic architecture, and resolution into ancestry-enriched effects

Meta-analyzing per-ancestry GWAS of 7,266 UK Biobank traits across six genetic ancestry groups adds 14,676 loci missed by European-only analysis, including ancestry-enriched CAMK2D and G6PD signals.

CHARR efficiently estimates contamination from DNA sequencing data

CHARR estimates DNA contamination from variant-level sequencing data, offering accurate results with reduced computational costs compared to existing methods.

Systematic single-variant and gene-based association testing of thousands of phenotypes in 426,370 UK Biobank exomes

The paper performs single-variant and gene-based association analyses of 4,529 phenotypes using exome data from 426,370 UK Biobank individuals, finding associations linked to variant frequency and deleteriousness.