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Semantic Scholar Open Access 2023 1125 sitasi

Plasma proteomic associations with genetics and health in the UK Biobank

B. Sun Joshua Chiou M. Traylor C. Benner Yi-Hsiang Hsu +51 lainnya
Lihat Sumber DOI

Abstrak

The Pharma Proteomics Project generates the largest open-access plasma proteomics dataset to date, offering insights into trans protein quantitative trait loci across multiple biological domains, and highlighting genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks. The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand–receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public–private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics^ 1 .

Topik & Kata Kunci

Medicine

Penulis (56)

B

B. Sun

J

Joshua Chiou

M

M. Traylor

C

C. Benner

Y

Yi-Hsiang Hsu

T

Tom G Richardson

P

P. Surendran

A

A. Mahajan

C

Chloe Robins

S

Steven G. Vasquez-Grinnell

L

Liping Hou

E

E. Kvikstad

O

O. Burren

J

Jonathan Davitte

K

Kyle L. Ferber

C

C. Gillies

Å

Åsa K Hedman

S

Sile Hu

T

Tinchi Lin

R

Rajesh Mikkilineni

R

R. Pendergrass

C

Corran Pickering

B

Bram Prins

D

D. Baird

C

Chia-Yen Chen

L

Lucas D. Ward

A

A. Deaton

S

Samantha Welsh

C

Carissa M. Willis

N

Nick Lehner

M

M. Arnold

M

Maria A. Wörheide

K

Karsten Suhre

G

G. Kastenmüller

A

A. Sethi

M

M. Cule

A

Anil Raj

H

H. Kang

L

L. Burkitt-Gray

E

E. Melamud

M

Mary Helen Black

E

E. Fauman

J

J. Howson

H

H. M. Kang

M

M. McCarthy

P

P. Nioi

S

S. Petrovski

R

Robert A. Scott

E

E. Smith

S

S. Szalma

D

D. Waterworth

L

L. Mitnaul

J

J. Szustakowski

B

Brad Gibson

M

Melissa R. Miller

C

Christopher D. Whelan

Format Sitasi

APA MLA BibTeX
Sun, B., Chiou, J., Traylor, M., Benner, C., Hsu, Y., Richardson, T.G. et al. (2023). Plasma proteomic associations with genetics and health in the UK Biobank. https://doi.org/10.1038/s41586-023-06592-6

Akses Cepat

Lihat di Sumber doi.org/10.1038/s41586-023-06592-6
Informasi Jurnal
Tahun Terbit
2023
Bahasa
en
Total Sitasi
1125×
Sumber Database
Semantic Scholar
DOI
10.1038/s41586-023-06592-6
Akses
Open Access ✓