Jeffrey P. Spence

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.

Coalescent-Based Time-Stratified Statistics Reveal Population Structure Dynamics using the Ancestral Recombination Graph

The paper introduces coalescent-based time-stratified statistics to accurately infer population structure dynamics using Ancestral Recombination Graphs.

Allele Frequencies at Recessive Disease Genes are Mainly Determined by Pleiotropic Effects in Heterozygotes

This study finds that allele frequencies at recessive disease genes are mainly shaped by pleiotropic effects in heterozygotes, not purely recessive selection.

Regulatory network topology and the genetic architecture of gene expression

The paper investigates how gene regulatory network topology influences the genetic architecture of gene expression, finding that local motifs and hub regulators shape heritability distribution.

Predicting the effect of CRISPR-Cas9-based epigenome editing

The paper trains machine learning models to predict gene expression from histone PTMs using ENCODE data and validates predictions with CRISPR-Cas9-based epigenome editing experiments.

High false sign rates in transcriptome-wide association studies

This study estimates the false sign rate in transcriptome-wide association studies (TWAS) for plasma proteins and complex traits, finding high discordance between predicted and expected gene effects.

Gene regulatory network structure informs the distribution of perturbation effects

The paper simulates gene regulatory networks and models perturbation effects to understand network structure and function.

Estimation of demography and mutation rates from one million haploid genomes

This paper introduces DR EVIL, a method to estimate mutation rates and demographic history from large haploid genome datasets, revealing mutation-rate heterogeneity and the impact of multiple mutation events on rare variants.

Haplotype Analysis Reveals Pleiotropic Disease Associations in the HLA Region

This study uses haplotype analysis to identify disease associations in the HLA region across 412,181 Finnish individuals, revealing pleiotropic patterns and 7,649 associations across 647 traits.

Causal modeling of gene effects from regulators to programs to traits: integration of genetic associations and Perturb-seq

The paper integrates genetic associations with Perturb-seq data to build causal graphs linking genes to traits through regulatory programs.

Specificity, length, and luck: How genes are prioritized by rare and common variant association studies

This paper compares how GWAS and rare variant burden tests prioritize genes for 209 traits in the UK Biobank, showing they focus on different genes due to distinct prioritization criteria.

Buffering and non-monotonic behavior of gene dosage response curves for human complex traits

The paper analyzes gene dosage response curves for human complex traits and shows that they exhibit biased direction of effect, developing a theoretical model to explain this phenomenon.

Large future genetic diversity losses are predicted even with habitat protection

The paper predicts significant future genetic diversity losses even with habitat protection using a spatio-temporal framework calibrated with genomic data from 29 species.

Diversity of ribosomes at the level of rRNA variation associated with human health and disease

This study identifies and characterizes rRNA variants in human tissues and cancer, revealing tissue-specific ribosome subtypes and cancer-specific ribosome variations.

Bayesian estimation of gene constraint from an evolutionary model with gene features

This paper introduces a Bayesian framework combining population genetics and machine learning to estimate gene constraint, improving accuracy for short genes and providing a flexible tool for gene-level property estimation.

Conditional frequency spectra as a tool for studying selection on complex traits in biobanks

The paper introduces conditional frequency spectra to study selection on complex traits in biobanks, finding evidence for stabilizing or purifying selection on GWAS-associated variants.

Stable population structure in Europe since the Iron Age, despite high mobility

This study analyzes ancient DNA from 204 individuals to show stable population structure in Europe despite high mobility during the historical period.

A Genetic History of Continuity and Mobility in the Iron Age Central Mediterranean

This study analyzes ancient genomes from the Iron Age central Mediterranean to explore population continuity and mobility, finding significant local contributions and diverse non-local ancestries.

The ENCODE Imputation Challenge: A critical assessment of methods for cross-cell type imputation of epigenomic profiles

The paper evaluates 23 imputation models for cross-cell type epigenomic data, finding quality assessment challenging due to distributional shifts, data availability, and redundant metrics.

Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations

The paper expands the stdpopsim species catalog and improves genome simulations by adding non-crossover recombination and species-specific annotations, making simulations more realistic for non-model organisms.

Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits

The paper tests for genetic interactions affecting causal variant effect sizes in gene expression and LDL-C across European and African American populations, finding significant evidence in gene expression but not LDL-C.

Limited overlap of eQTLs and GWAS hits due to systematic differences in discovery

GWAS hits (44 UK Biobank traits) and GTEx v8 cis-eQTLs (38 tissues) differ systematically: eQTLs cluster near transcription start sites of weakly constrained genes; GWAS hits favour constrained, multifunctional genes.

A flexible modeling and inference framework for estimating variant effect sizes from GWAS summary statistics

This paper introduces a framework for estimating variant effect sizes from GWAS summary statistics, improving polygenic score accuracy by jointly inferring individual variant effects and distributional properties.

Shared heritability of face and brain shape distinct from cognitive traits

This study identifies shared genetic loci influencing brain and facial shape, distinct from cognitive traits, suggesting a developmental link between brain and face formation.

A Likelihood-Free Inference Framework for Population Genetic Data using Exchangeable Neural Networks

This paper introduces an exchangeable neural network framework for likelihood-free inference in population genetics, demonstrating superior performance on recombination hotspot testing.