Konrad J. Karczewski

The mutational constraint spectrum quantified from variation in 141,456 humans

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the f...

Analysis of protein-coding genetic variation in 60,706 humans

Quantifying prion disease penetrance using large population control cohorts

Large genomic reference data sets reveal a spectrum of pathogenicity in the prion protein gene and provide genetic validation for a therapeutic strategy in prion disease.

A structural variation reference for medical and population genetics

Transcript expression-aware annotation improves rare variant interpretation

Characterising the loss-of-function impact of 5’ untranslated region variants in 15,708 individuals

Abstract Upstream open reading frames (uORFs) are tissue-specific cis -regulators of protein translation. Isolated reports have shown that variants that create or disrupt uORFs ...

The effect of LRRK2 loss-of-function variants in humans

Abstract Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be ...

Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum

There is a limited understanding about the impact of rare protein-truncating variants across multiple phenotypes. We explore the impact of this class of variants on 13 quantitat...

Mendelian randomization of blood lipids for coronary heart disease

The genetic findings support a causal effect of triglycerides on CHD risk, but a causal role for HDL-C, though possible, remains less certain.