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DOAJ Open Access 2023

Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits

Andrew A. Brown Juan J. Fernandez-Tajes Mun-gwan Hong Caroline A. Brorsson Robert W. Koivula +56 lainnya
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Abstrak

Abstract We evaluate the shared genetic regulation of mRNA molecules, proteins and metabolites derived from whole blood from 3029 human donors. We find abundant allelic heterogeneity, where multiple variants regulate a particular molecular phenotype, and pleiotropy, where a single variant associates with multiple molecular phenotypes over multiple genomic regions. The highest proportion of share genetic regulation is detected between gene expression and proteins (66.6%), with a further median shared genetic associations across 49 different tissues of 78.3% and 62.4% between plasma proteins and gene expression. We represent the genetic and molecular associations in networks including 2828 known GWAS variants, showing that GWAS variants are more often connected to gene expression in trans than other molecular phenotypes in the network. Our work provides a roadmap to understanding molecular networks and deriving the underlying mechanism of action of GWAS variants using different molecular phenotypes in an accessible tissue.

Topik & Kata Kunci

Science

Penulis (61)

A

Andrew A. Brown

J

Juan J. Fernandez-Tajes

M

Mun-gwan Hong

C

Caroline A. Brorsson

R

Robert W. Koivula

D

David Davtian

T

Théo Dupuis

A

Ambra Sartori

T

Theodora-Dafni Michalettou

I

Ian M. Forgie

J

Jonathan Adam

K

Kristine H. Allin

R

Robert Caiazzo

H

Henna Cederberg

F

Federico De Masi

P

Petra J. M. Elders

G

Giuseppe N. Giordano

M

Mark Haid

T

Torben Hansen

T

Tue H. Hansen

A

Andrew T. Hattersley

A

Alison J. Heggie

C

Cédric Howald

A

Angus G. Jones

T

Tarja Kokkola

M

Markku Laakso

A

Anubha Mahajan

A

Andrea Mari

T

Timothy J. McDonald

D

Donna McEvoy

M

Miranda Mourby

P

Petra B. Musholt

B

Birgitte Nilsson

F

Francois Pattou

D

Deborah Penet

V

Violeta Raverdy

M

Martin Ridderstråle

L

Luciana Romano

F

Femke Rutters

S

Sapna Sharma

H

Harriet Teare

L

Leen ‘t Hart

K

Konstantinos D. Tsirigos

J

Jagadish Vangipurapu

H

Henrik Vestergaard

S

Søren Brunak

P

Paul W. Franks

G

Gary Frost

H

Harald Grallert

B

Bernd Jablonka

M

Mark I. McCarthy

I

Imre Pavo

O

Oluf Pedersen

H

Hartmut Ruetten

M

Mark Walker

T

The DIRECT Consortium

J

Jerzy Adamski

J

Jochen M. Schwenk

E

Ewan R. Pearson

E

Emmanouil T. Dermitzakis

A

Ana Viñuela

Format Sitasi

APA MLA BibTeX
Brown, A.A., Fernandez-Tajes, J.J., Hong, M., Brorsson, C.A., Koivula, R.W., Davtian, D. et al. (2023). Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits. https://doi.org/10.1038/s41467-023-40569-3

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Lihat di Sumber doi.org/10.1038/s41467-023-40569-3
Informasi Jurnal
Tahun Terbit
2023
Sumber Database
DOAJ
DOI
10.1038/s41467-023-40569-3
Akses
Open Access ✓