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 …

Advancing human genetics research and drug discovery through exome sequencing of the UK Biobank

JD Szustakowski, S Balasubramanian, E Kvikstad… - Nature …, 2021 - nature.com
Abstract The UK Biobank Exome Sequencing Consortium (UKB-ESC) is a private–public
partnership between the UK Biobank (UKB) and eight biopharmaceutical companies that …

Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis

K Ishigaki, S Sakaue, C Terao, Y Luo, K Sonehara… - Nature …, 2022 - nature.com
Rheumatoid arthritis (RA) is a highly heritable complex disease with unknown etiology. Multi-
ancestry genetic research of RA promises to improve power to detect genetic signals, fine …

Host genetic factors determining COVID-19 susceptibility and severity

TP Velavan, SR Pallerla, J Rüter, Y Augustin… - …, 2021 - thelancet.com
The COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2
(SARS-CoV-2) poses an unprecedented challenge to humanity. SARS-CoV-2 infections …

From GWAS to function: using functional genomics to identify the mechanisms underlying complex diseases

E Cano-Gamez, G Trynka - Frontiers in genetics, 2020 - frontiersin.org
Genome-wide association studies (GWAS) have successfully mapped thousands of loci
associated with complex traits. These associations could reveal the molecular mechanisms …

Large-scale sequencing identifies multiple genes and rare variants associated with Crohn's disease susceptibility

A Sazonovs, CR Stevens, GR Venkataraman, K Yuan… - Nature …, 2022 - nature.com
Genome-wide association studies (GWASs) have identified hundreds of loci associated with
Crohn's disease (CD). However, as with all complex diseases, robust identification of the …

[HTML][HTML] Mapping ICD-10 and ICD-10-CM codes to phecodes: workflow development and initial evaluation

P Wu, A Gifford, X Meng, X Li, H Campbell… - JMIR medical …, 2019 - medinform.jmir.org
Background: The phecode system was built upon the International Classification of
Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) for phenome-wide association …

Immune disease risk variants regulate gene expression dynamics during CD4+ T cell activation

B Soskic, E Cano-Gamez, DJ Smyth, K Ambridge… - Nature …, 2022 - nature.com
During activation, T cells undergo extensive gene expression changes that shape the
properties of cells to exert their effector function. Understanding the regulation of this …

Protein kinases: drug targets for immunological disorders

L Castelo-Soccio, H Kim, M Gadina… - Nature Reviews …, 2023 - nature.com
Protein kinases play a major role in cellular activation processes, including signal
transduction by diverse immunoreceptors. Given their roles in cell growth and death and in …

Autoimmune pathways in mice and humans are blocked by pharmacological stabilization of the TYK2 pseudokinase domain

JR Burke, L Cheng, KM Gillooly, J Strnad… - Science translational …, 2019 - science.org
TYK2 is a nonreceptor tyrosine kinase involved in adaptive and innate immune responses. A
deactivating coding variant has previously been shown to prevent receptor-stimulated …