Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
| Title: | Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits |
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| Authors: | Brown AA; Fernandez-Tajes JJ; Hong M-G; Brorsson CA; Koivula RW; Davtian D; Dupuis T; Sartori A; Michalettou T-D; Forgie IM; Adam J; Allin KH; Caiazzo R; Cederberg H; De Masi F; Elders PJM; Giordano GN; Haid M; Hansen T; Hansen TH; Hattersley AT; Heggie AJ; Howald C; Jones AG; Kokkola T; Laakso M; Mahajan A; Mari A; McDonald TJ; McEvoy D; Mourby M; Musholt PB; Nilsson B; Pattou F; Penet D; Raverdy V; Ridderstrale M; Romano L; Rutters F; Sharma S; Teare H; 't Hart L; Tsirigos KD; Vangipurapu J; Vestergaard H; Brunak S; Franks PW; Frost G; Grallert H; Jablonka B; McCarthy MI; Pavo I; Pedersen O; Ruetten H; Walker M; Adragni K; Allesoe RLL; Artati AA; Arumugam M; Atabaki-Pasdar N; Baltauss T; Banasik K; Barnett AL; Baum P; Bell JD; Beulens JW; Bianzano SB; Bizzotto R; Bonnefond A; Cabrelli L; Dale M; Dawed AY; de Preville N; Dekkers KF; Deshmukh HA; Dings C; Donnelly L; Dutta A; Ehrhardt B; Engelbrechtsen L; Eriksen R; Fan Y; Ferrer J; Fitipaldi H; Forman A; Fritsche A; Froguel P; Gassenhuber J; Gough S; Graefe-Mody U; Grempler R; Groeneveld L; Groop L; Gudmundsdottir V; Gupta R; Hennige AMH; Hill AV; Holl RW; Hudson M; Jacobsen UP; Jennison C; Johansen J; Jonsson A; Karaderi T; Kaye J; Kennedy G; Klintenberg M; Kuulasmaa T; Lehr T; Loftus H; Lundgaard ATT; Mazzoni G; McRobert N; McVittie I; Nice R; Nicolay C; Nijpels G; Palmer CN; Pedersen HK; Perry MH; Pomares-Millan H; Prehn CP; Ramisch A; Rasmussen S; Robertson N; Rodriquez M; Sackett P; Scherer N; Shah N; Sihinevich I; Slieker RC; Sondertoft NB; Steckel-Hamann B; Thomas MK; Thomas CEE; Thomas ELL; Thorand B; Thorne CE; Tillner J; Tura A; Uhlen M; van Leeuwen N; van Oort S; Verkindt H; Vogt J; Wad Sackett PW; Wesolowska-Andersen A; Whitcher B; White MW; Adamski J; Schwenk JM; Pearson ER; Dermitzakis ET; Vinuela A |
| Source: | Nature Communications, December 2023 |
| Publisher Information: | Nature Research |
| Publication Year: | 2023 |
| Collection: | Newcastle University Library ePrints Service |
| Description: | © 2023, Springer Nature Limited.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. |
| Document Type: | article in journal/newspaper |
| File Description: | application/pdf |
| Language: | unknown |
| Relation: | https://eprints.ncl.ac.uk/293073; https://eprints.ncl.ac.uk/fulltext.aspx?url=293073/5ACB33E7-F1DB-4BFB-9C63-5050B114194E.pdf&pub_id=293073 |
| Availability: | https://eprints.ncl.ac.uk/293073 |
| Rights: | https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.9097E487 |
| Database: | BASE |