Responsible use of polygenic risk scores in the clinic: potential benefits, risks and gaps

Nature medicine, 2021 - nature.com
Polygenic risk scores (PRSs) aggregate the many small effects of alleles across the human
genome to estimate the risk of a disease or disease-related trait for an individual. The …

The genetic architecture of Parkinson's disease

C Blauwendraat, MA Nalls, AB Singleton - The Lancet Neurology, 2020 - thelancet.com
Parkinson's disease is a complex neurodegenerative disorder for which both rare and
common genetic variants contribute to disease risk, onset, and progression. Mutations in …

An integrated cell atlas of the lung in health and disease

L Sikkema, C Ramírez-Suástegui, DC Strobl… - Nature medicine, 2023 - nature.com
Single-cell technologies have transformed our understanding of human tissues. Yet, studies
typically capture only a limited number of donors and disagree on cell type definitions …

CZ CELLxGENE Discover: A single-cell data platform for scalable exploration, analysis and modeling of aggregated data

CZI Cell Science Program, S Abdulla… - Nucleic Acids …, 2024 - academic.oup.com
Hundreds of millions of single cells have been analyzed using high-throughput
transcriptomic methods. The cumulative knowledge within these datasets provides an …

Underspecification presents challenges for credibility in modern machine learning

A D'Amour, K Heller, D Moldovan, B Adlam… - Journal of Machine …, 2022 - jmlr.org
Machine learning (ML) systems often exhibit unexpectedly poor behavior when they are
deployed in real-world domains. We identify underspecification in ML pipelines as a key …

Genome-wide analysis provides genetic evidence that ACE2 influences COVID-19 risk and yields risk scores associated with severe disease

JE Horowitz, JA Kosmicki, A Damask, D Sharma… - Nature …, 2022 - nature.com
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human host cells
via angiotensin-converting enzyme 2 (ACE2) and causes coronavirus disease 2019 (COVID …

The MRC IEU OpenGWAS data infrastructure

B Elsworth, M Lyon, T Alexander, Y Liu, P Matthews… - BioRxiv, 2020 - biorxiv.org
Data generated by genome-wide association studies (GWAS) are growing fast with the
linkage of biobank samples to health records, and expanding capture of high-dimensional …

Systematic single-variant and gene-based association testing of thousands of phenotypes in 394,841 UK Biobank exomes

KJ Karczewski, M Solomonson, KR Chao, JK Goodrich… - Cell Genomics, 2022 - cell.com
Genome-wide association studies have successfully discovered thousands of common
variants associated with human diseases and traits, but the landscape of rare variations in …

An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci

E Mountjoy, EM Schmidt, M Carmona… - Nature …, 2021 - nature.com
Genome-wide association studies (GWASs) have identified many variants associated with
complex traits, but identifying the causal gene (s) is a major challenge. In the present study …

Polygenic risk scores: from research tools to clinical instruments

CM Lewis, E Vassos - Genome medicine, 2020 - Springer
Genome-wide association studies have shown unequivocally that common complex
disorders have a polygenic genetic architecture and have enabled researchers to identify …