Incomplete penetrance and variable expressivity: from clinical studies to population cohorts

R Kingdom, CF Wright - Frontiers in Genetics, 2022‏ - frontiersin.org
The same genetic variant found in different individuals can cause a range of diverse
phenotypes, from no discernible clinical phenotype to severe disease, even among related …

Using human genetics to improve safety assessment of therapeutics

KJ Carss, AM Deaton, A Del Rio-Espinola… - Nature Reviews Drug …, 2023‏ - nature.com
Human genetics research has discovered thousands of proteins associated with complex
and rare diseases. Genome-wide association studies (GWAS) and studies of Mendelian …

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

KJ Karczewski, LC Francioli, G Tiao, BB Cummings… - Nature, 2020‏ - nature.com
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 …

Leveraging base-pair mammalian constraint to understand genetic variation and human disease

PF Sullivan, JRS Meadows, S Gazal, BDN Phan, X Li… - Science, 2023‏ - science.org
Thousands of genomic regions have been associated with heritable human diseases, but
attempts to elucidate biological mechanisms are impeded by an inability to discern which …

Variation across 141,456 human exomes and genomes reveals the spectrum of loss-of-function intolerance across human protein-coding genes

KJ Karczewski, LC Francioli, G Tiao, BB Cummings… - biorxiv, 2019‏ - biorxiv.org
Genetic variants that inactivate protein-coding genes are a powerful source of information
about the phenotypic consequences of gene disruption: genes critical for an organism's …

Functional map** and annotation of genetic associations with FUMA

K Watanabe, E Taskesen, A Van Bochoven… - Nature …, 2017‏ - nature.com
A main challenge in genome-wide association studies (GWAS) is to pinpoint possible causal
variants. Results from GWAS typically do not directly translate into causal variants because …

Common variants in Alzheimer's disease and risk stratification by polygenic risk scores

I De Rojas, S Moreno-Grau, N Tesi… - Nature …, 2021‏ - nature.com
Genetic discoveries of Alzheimer's disease are the drivers of our understanding, and
together with polygenetic risk stratification can contribute towards planning of feasible and …

Discovery of 42 genome-wide significant loci associated with dyslexia

C Doust, P Fontanillas, E Eising, SD Gordon, Z Wang… - Nature …, 2022‏ - nature.com
Reading and writing are crucial life skills but roughly one in ten children are affected by
dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up …

[HTML][HTML] Genomic analysis in the age of human genome sequencing

T Lappalainen, AJ Scott, M Brandt, IM Hall - Cell, 2019‏ - cell.com
Affordable genome sequencing technologies promise to revolutionize the field of human
genetics by enabling comprehensive studies that interrogate all classes of genome …

Rare-variant collapsing analyses for complex traits: guidelines and applications

G Povysil, S Petrovski, J Hostyk, V Aggarwal… - Nature Reviews …, 2019‏ - nature.com
The first phase of genome-wide association studies (GWAS) assessed the role of common
variation in human disease. Advances optimizing and economizing high-throughput …