From target discovery to clinical drug development with human genetics

K Trajanoska, C Bhérer, D Taliun, S Zhou, JB Richards… - Nature, 2023 - nature.com
The substantial investments in human genetics and genomics made over the past three
decades were anticipated to result in many innovative therapies. Here we investigate the …

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 …

[HTML][HTML] FinnGen provides genetic insights from a well-phenotyped isolated population

MI Kurki, J Karjalainen, P Palta, TP Sipilä… - Nature, 2023 - nature.com
Population isolates such as those in Finland benefit genetic research because deleterious
alleles are often concentrated on a small number of low-frequency variants (0.1%≤ minor …

FinnGen: Unique genetic insights from combining isolated population and national health register data

MI Kurki, J Karjalainen, P Palta, TP Sipilä… - medrxiv, 2022 - medrxiv.org
Population isolates such as Finland provide benefits in genetic studies because the allelic
spectrum of damaging alleles in any gene is often concentrated on a small number of low …

[HTML][HTML] 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 …

Metastasis from the tumor interior and necrotic core formation are regulated by breast cancer-derived angiopoietin-like 7

A Yamamoto, Y Huang, BA Krajina… - Proceedings of the …, 2023 - National Acad Sciences
Necrosis in the tumor interior is a common feature of aggressive cancers that is associated
with poor clinical prognosis and the development of metastasis. How the necrotic core …

[HTML][HTML] Significant sparse polygenic risk scores across 813 traits in UK Biobank

Y Tanigawa, J Qian, G Venkataraman… - PLoS …, 2022 - journals.plos.org
We present a systematic assessment of polygenic risk score (PRS) prediction across more
than 1,500 traits using genetic and phenotype data in the UK Biobank. We report 813 sparse …

Extraocular, periocular, and intraocular routes for sustained drug delivery for glaucoma

UB Kompella, RR Hartman, MA Patil - Progress in retinal and eye research, 2021 - Elsevier
Although once daily anti-glaucoma drug therapy is a current clinical reality, most therapies
require multiple dosing and there is an unmet need to develop convenient, safe, and …

The genetic basis for adult onset glaucoma: recent advances and future directions

Z Wang, JL Wiggs, T Aung, AP Khawaja… - Progress in Retinal and …, 2022 - Elsevier
Glaucoma, a diverse group of eye disorders that results in the degeneration of retinal
ganglion cells, is the world's leading cause of irreversible blindness. Apart from age and …

EFEMP1 rare variants cause familial juvenile‐onset open‐angle glaucoma

ERA Collantes, MS Delfin, B Fan… - Human …, 2022 - Wiley Online Library
Juvenile open‐angle glaucoma (JOAG) is a severe type of glaucoma with onset before age
40 and dominant inheritance. Using exome sequencing we identified 3 independent families …