Hakhamanesh Mostafavi

A Litmus Test for Confounding in Polygenic Scores

This paper introduces PGSUS, a method to assess the influence of stratification and assortative mating effects on polygenic scores, revealing that direct genetic effects often contribute little to PGS variation.

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.

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.

Simple scaling laws control the genetic architectures of human complex traits

The paper develops a probabilistic model to explain genetic architectures of complex traits using scaling laws, finding that traits share similar selection coefficients but differ in scaling parameters.

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.

Bayesian model comparison for rare variant association studies

The paper introduces a Bayesian model comparison approach, MRP, for rare variant association studies using summary statistics, demonstrating improved power and discovery of gene-trait associations across multiple phenotypes.

Variable prediction accuracy of polygenic scores within an ancestry group

The paper shows that polygenic scores have varying prediction accuracy within a single ancestry group based on factors like age, sex, and GWAS study design.

Measuring \"intolerance to mutation\" in human genetics

The paper explains that population genetic measures like pLI reflect selection on heterozygotes, not dominance or haploinsufficiency.