Standard
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits. / Brown, Andrew A.; Fernandez-Tajes, Juan J.; Hong, Mun gwan; Brorsson, Caroline A.; Koivula, Robert W.; Davtian, David; Dupuis, Théo; Sartori, Ambra; Michalettou, Theodora Dafni; Forgie, Ian M.; Adam, Jonathan; Allin, Kristine H.; Caiazzo, Robert; Cederberg, Henna; De Masi, Federico; Elders, Petra J.M.; Giordano, Giuseppe N.; Haid, Mark; Hansen, Torben; Hansen, Tue H.; Hattersley, Andrew T.; Heggie, Alison J.; Howald, Cédric; Jones, Angus G.; Kokkola, Tarja; Laakso, Markku; Mahajan, Anubha; Mari, Andrea; McDonald, Timothy J.; McEvoy, Donna; Mourby, Miranda; Musholt, Petra B.; Nilsson, Birgitte; Pattou, Francois; Penet, Deborah; Raverdy, Violeta; Ridderstråle, Martin; Romano, Luciana; Rutters, Femke; Sharma, Sapna; Teare, Harriet; ‘t Hart, Leen; Tsirigos, Konstantinos D.; Vangipurapu, Jagadish; Vestergaard, Henrik; Brunak, Søren; Franks, Paul W.; Frost, Gary; Grallert, Harald; Jablonka, Bernd; McCarthy, Mark I.; Pavo, Imre; Pedersen, Oluf; Ruetten, Hartmut; Walker, Mark; Adragni, Kofi; Allesøe, Rosa Lundbye L.; Artati, Anna A.; Arumugam, Manimozhiyan; Atabaki-Pasdar, Naeimeh; Baltauss, Tania; Banasik, Karina; Barnett, Anna L.; Baum, Patrick; Bell, Jimmy D.; Beulens, Joline W.; Bianzano, Susanna B.; Bizzotto, Roberto; Bonnefond, Amelie; Cabrelli, Louise; Dale, Matilda; Dawed, Adem Y.; de Preville, Nathalie; Dekkers, Koen F.; Deshmukh, Harshal A.; Dings, Christiane; Donnelly, Louise; Dutta, Avirup; Ehrhardt, Beate; Engelbrechtsen, Line; Eriksen, Rebeca; Fan, Yong; Ferrer, Jorge; Fitipaldi, Hugo; Forman, Annemette; Fritsche, Andreas; Froguel, Philippe; Gassenhuber, Johann; Gough, Stephen; Graefe-Mody, Ulrike; Grempler, Rolf; Groeneveld, Lenka; Groop, Leif; Gudmundsdóttir, Valborg; Gupta, Ramneek; Hennige, Anita M.H.; Hill, Anita V.; Holl, Reinhard W.; Hudson, Michelle; Jacobsen, Ulrik Plesner; Jennison, Christopher; Johansen, Joachim; Jonsson, Anna; Karaderi, Tugce; Kaye, Jane; Kennedy, Gwen; Klintenberg, Maria; Kuulasmaa, Teemu; Lehr, Thorsten; Loftus, Heather; Lundgaard, Agnete Troen T.; Mazzoni, Gianluca; McRobert, Nicky; McVittie, Ian; Nice, Rachel; Nicolay, Claudia; Nijpels, Giel; Palmer, Colin N.; Pedersen, Helle K.; Perry, Mandy H.; Pomares-Millan, Hugo; Prehn, Cornelia P.; Ramisch, Anna; Rasmussen, Simon; Robertson, Neil; Rodriquez, Marianne; Sackett, Peter; Scherer, Nina; Shah, Nisha; Sihinevich, Iryna; Slieker, Roderick C.; Sondertoft, Nadja B.; Steckel-Hamann, Birgit; Thomas, Melissa K.; Thomas, Cecilia Engel E.; Thomas, Elizabeth Louise L.; Thorand, Barbara; Thorne, Claire E.; Tillner, Joachim; Tura, Andrea; Uhlen, Mathias; van Leeuwen, Nienke; van Oort, Sabine; Verkindt, Helene; Vogt, Josef; Wad Sackett, Peter W.; Wesolowska-Andersen, Agata; Whitcher, Brandon; White, Margaret W.; Adamski, Jerzy; Schwenk, Jochen M.; Pearson, Ewan R.; Dermitzakis, Emmanouil T.; Viñuela, Ana.
In:
Nature Communications, Vol. 14, 5062, 2023.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Brown, AA, Fernandez-Tajes, JJ, Hong, MG, Brorsson, CA, Koivula, RW, Davtian, D, Dupuis, T, Sartori, A, Michalettou, TD, 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, Ridderstråle, 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, Allesøe, 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, Gudmundsdóttir, 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 & Viñuela, A 2023, '
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits',
Nature Communications, vol. 14, 5062.
https://doi.org/10.1038/s41467-023-40569-3
APA
Brown, A. A., Fernandez-Tajes, J. J., Hong, M. G., Brorsson, C. A., Koivula, R. W., Davtian, D., Dupuis, T., Sartori, A., Michalettou, T. D., Forgie, I. M., Adam, J., Allin, K. H., Caiazzo, R., Cederberg, H., De Masi, F., Elders, P. J. M., Giordano, G. N., Haid, M.
, Hansen, T., ... Viñuela, A. (2023).
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits.
Nature Communications,
14, [5062].
https://doi.org/10.1038/s41467-023-40569-3
Vancouver
Brown AA, Fernandez-Tajes JJ, Hong MG, Brorsson CA, Koivula RW, Davtian D et al.
Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits.
Nature Communications. 2023;14. 5062.
https://doi.org/10.1038/s41467-023-40569-3
Author
Brown, Andrew A. ; Fernandez-Tajes, Juan J. ; Hong, Mun gwan ; Brorsson, Caroline A. ; Koivula, Robert W. ; Davtian, David ; Dupuis, Théo ; Sartori, Ambra ; Michalettou, Theodora Dafni ; Forgie, Ian M. ; Adam, Jonathan ; Allin, Kristine H. ; Caiazzo, Robert ; Cederberg, Henna ; De Masi, Federico ; Elders, Petra J.M. ; Giordano, Giuseppe N. ; Haid, Mark ; Hansen, Torben ; Hansen, Tue H. ; Hattersley, Andrew T. ; Heggie, Alison J. ; Howald, Cédric ; Jones, Angus G. ; Kokkola, Tarja ; Laakso, Markku ; Mahajan, Anubha ; Mari, Andrea ; McDonald, Timothy J. ; McEvoy, Donna ; Mourby, Miranda ; Musholt, Petra B. ; Nilsson, Birgitte ; Pattou, Francois ; Penet, Deborah ; Raverdy, Violeta ; Ridderstråle, Martin ; Romano, Luciana ; Rutters, Femke ; Sharma, Sapna ; Teare, Harriet ; ‘t Hart, Leen ; Tsirigos, Konstantinos D. ; Vangipurapu, Jagadish ; Vestergaard, Henrik ; Brunak, Søren ; Franks, Paul W. ; Frost, Gary ; Grallert, Harald ; Jablonka, Bernd ; McCarthy, Mark I. ; Pavo, Imre ; Pedersen, Oluf ; Ruetten, Hartmut ; Walker, Mark ; Adragni, Kofi ; Allesøe, Rosa Lundbye L. ; Artati, Anna A. ; Arumugam, Manimozhiyan ; Atabaki-Pasdar, Naeimeh ; Baltauss, Tania ; Banasik, Karina ; Barnett, Anna L. ; Baum, Patrick ; Bell, Jimmy D. ; Beulens, Joline W. ; Bianzano, Susanna B. ; Bizzotto, Roberto ; Bonnefond, Amelie ; Cabrelli, Louise ; Dale, Matilda ; Dawed, Adem Y. ; de Preville, Nathalie ; Dekkers, Koen F. ; Deshmukh, Harshal A. ; Dings, Christiane ; Donnelly, Louise ; Dutta, Avirup ; Ehrhardt, Beate ; Engelbrechtsen, Line ; Eriksen, Rebeca ; Fan, Yong ; Ferrer, Jorge ; Fitipaldi, Hugo ; Forman, Annemette ; Fritsche, Andreas ; Froguel, Philippe ; Gassenhuber, Johann ; Gough, Stephen ; Graefe-Mody, Ulrike ; Grempler, Rolf ; Groeneveld, Lenka ; Groop, Leif ; Gudmundsdóttir, Valborg ; Gupta, Ramneek ; Hennige, Anita M.H. ; Hill, Anita V. ; Holl, Reinhard W. ; Hudson, Michelle ; Jacobsen, Ulrik Plesner ; Jennison, Christopher ; Johansen, Joachim ; Jonsson, Anna ; Karaderi, Tugce ; Kaye, Jane ; Kennedy, Gwen ; Klintenberg, Maria ; Kuulasmaa, Teemu ; Lehr, Thorsten ; Loftus, Heather ; Lundgaard, Agnete Troen T. ; Mazzoni, Gianluca ; McRobert, Nicky ; McVittie, Ian ; Nice, Rachel ; Nicolay, Claudia ; Nijpels, Giel ; Palmer, Colin N. ; Pedersen, Helle K. ; Perry, Mandy H. ; Pomares-Millan, Hugo ; Prehn, Cornelia P. ; Ramisch, Anna ; Rasmussen, Simon ; Robertson, Neil ; Rodriquez, Marianne ; Sackett, Peter ; Scherer, Nina ; Shah, Nisha ; Sihinevich, Iryna ; Slieker, Roderick C. ; Sondertoft, Nadja B. ; Steckel-Hamann, Birgit ; Thomas, Melissa K. ; Thomas, Cecilia Engel E. ; Thomas, Elizabeth Louise L. ; Thorand, Barbara ; Thorne, Claire E. ; Tillner, Joachim ; Tura, Andrea ; Uhlen, Mathias ; van Leeuwen, Nienke ; van Oort, Sabine ; Verkindt, Helene ; Vogt, Josef ; Wad Sackett, Peter W. ; Wesolowska-Andersen, Agata ; Whitcher, Brandon ; White, Margaret W. ; Adamski, Jerzy ; Schwenk, Jochen M. ; Pearson, Ewan R. ; Dermitzakis, Emmanouil T. ; Viñuela, Ana. / Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits. In: Nature Communications. 2023 ; Vol. 14.
Bibtex
@article{4f12f78e73e54907ab3765b10c4468ee,
title = "Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits",
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.",
author = "Brown, {Andrew A.} and Fernandez-Tajes, {Juan J.} and Hong, {Mun gwan} and Brorsson, {Caroline A.} and Koivula, {Robert W.} and David Davtian and Th{\'e}o Dupuis and Ambra Sartori and Michalettou, {Theodora Dafni} and Forgie, {Ian M.} and Jonathan Adam and Allin, {Kristine H.} and Robert Caiazzo and Henna Cederberg and {De Masi}, Federico and Elders, {Petra J.M.} and Giordano, {Giuseppe N.} and Mark Haid and Torben Hansen and Hansen, {Tue H.} and Hattersley, {Andrew T.} and Heggie, {Alison J.} and C{\'e}dric Howald and Jones, {Angus G.} and Tarja Kokkola and Markku Laakso and Anubha Mahajan and Andrea Mari and McDonald, {Timothy J.} and Donna McEvoy and Miranda Mourby and Musholt, {Petra B.} and Birgitte Nilsson and Francois Pattou and Deborah Penet and Violeta Raverdy and Martin Ridderstr{\aa}le and Luciana Romano and Femke Rutters and Sapna Sharma and Harriet Teare and {{\textquoteleft}t Hart}, Leen and Tsirigos, {Konstantinos D.} and Jagadish Vangipurapu and Henrik Vestergaard and S{\o}ren Brunak and Franks, {Paul W.} and Gary Frost and Harald Grallert and Bernd Jablonka and McCarthy, {Mark I.} and Imre Pavo and Oluf Pedersen and Hartmut Ruetten and Mark Walker and Kofi Adragni and Alles{\o}e, {Rosa Lundbye L.} and Artati, {Anna A.} and Manimozhiyan Arumugam and Naeimeh Atabaki-Pasdar and Tania Baltauss and Karina Banasik and Barnett, {Anna L.} and Patrick Baum and Bell, {Jimmy D.} and Beulens, {Joline W.} and Bianzano, {Susanna B.} and Roberto Bizzotto and Amelie Bonnefond and Louise Cabrelli and Matilda Dale and Dawed, {Adem Y.} and {de Preville}, Nathalie and Dekkers, {Koen F.} and Deshmukh, {Harshal A.} and Christiane Dings and Louise Donnelly and Avirup Dutta and Beate Ehrhardt and Line Engelbrechtsen and Rebeca Eriksen and Yong Fan and Jorge Ferrer and Hugo Fitipaldi and Annemette Forman and Andreas Fritsche and Philippe Froguel and Johann Gassenhuber and Stephen Gough and Ulrike Graefe-Mody and Rolf Grempler and Lenka Groeneveld and Leif Groop and Valborg Gudmundsd{\'o}ttir and Ramneek Gupta and Hennige, {Anita M.H.} and Hill, {Anita V.} and Holl, {Reinhard W.} and Michelle Hudson and Jacobsen, {Ulrik Plesner} and Christopher Jennison and Joachim Johansen and Anna Jonsson and Tugce Karaderi and Jane Kaye and Gwen Kennedy and Maria Klintenberg and Teemu Kuulasmaa and Thorsten Lehr and Heather Loftus and Lundgaard, {Agnete Troen T.} and Gianluca Mazzoni and Nicky McRobert and Ian McVittie and Rachel Nice and Claudia Nicolay and Giel Nijpels and Palmer, {Colin N.} and Pedersen, {Helle K.} and Perry, {Mandy H.} and Hugo Pomares-Millan and Prehn, {Cornelia P.} and Anna Ramisch and Simon Rasmussen and Neil Robertson and Marianne Rodriquez and Peter Sackett and Nina Scherer and Nisha Shah and Iryna Sihinevich and Slieker, {Roderick C.} and Sondertoft, {Nadja B.} and Birgit Steckel-Hamann and Thomas, {Melissa K.} and Thomas, {Cecilia Engel E.} and Thomas, {Elizabeth Louise L.} and Barbara Thorand and Thorne, {Claire E.} and Joachim Tillner and Andrea Tura and Mathias Uhlen and {van Leeuwen}, Nienke and {van Oort}, Sabine and Helene Verkindt and Josef Vogt and {Wad Sackett}, {Peter W.} and Agata Wesolowska-Andersen and Brandon Whitcher and White, {Margaret W.} and Jerzy Adamski and Schwenk, {Jochen M.} and Pearson, {Ewan R.} and Dermitzakis, {Emmanouil T.} and Ana Vi{\~n}uela",
note = "Publisher Copyright: {\textcopyright} 2023, Springer Nature Limited.",
year = "2023",
doi = "10.1038/s41467-023-40569-3",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",
}
RIS
TY - JOUR
T1 - Genetic analysis of blood molecular phenotypes reveals common properties in the regulatory networks affecting complex traits
AU - Brown, Andrew A.
AU - Fernandez-Tajes, Juan J.
AU - Hong, Mun gwan
AU - Brorsson, Caroline A.
AU - Koivula, Robert W.
AU - Davtian, David
AU - Dupuis, Théo
AU - Sartori, Ambra
AU - Michalettou, Theodora Dafni
AU - Forgie, Ian M.
AU - Adam, Jonathan
AU - Allin, Kristine H.
AU - Caiazzo, Robert
AU - Cederberg, Henna
AU - De Masi, Federico
AU - Elders, Petra J.M.
AU - Giordano, Giuseppe N.
AU - Haid, Mark
AU - Hansen, Torben
AU - Hansen, Tue H.
AU - Hattersley, Andrew T.
AU - Heggie, Alison J.
AU - Howald, Cédric
AU - Jones, Angus G.
AU - Kokkola, Tarja
AU - Laakso, Markku
AU - Mahajan, Anubha
AU - Mari, Andrea
AU - McDonald, Timothy J.
AU - McEvoy, Donna
AU - Mourby, Miranda
AU - Musholt, Petra B.
AU - Nilsson, Birgitte
AU - Pattou, Francois
AU - Penet, Deborah
AU - Raverdy, Violeta
AU - Ridderstråle, Martin
AU - Romano, Luciana
AU - Rutters, Femke
AU - Sharma, Sapna
AU - Teare, Harriet
AU - ‘t Hart, Leen
AU - Tsirigos, Konstantinos D.
AU - Vangipurapu, Jagadish
AU - Vestergaard, Henrik
AU - Brunak, Søren
AU - Franks, Paul W.
AU - Frost, Gary
AU - Grallert, Harald
AU - Jablonka, Bernd
AU - McCarthy, Mark I.
AU - Pavo, Imre
AU - Pedersen, Oluf
AU - Ruetten, Hartmut
AU - Walker, Mark
AU - Adragni, Kofi
AU - Allesøe, Rosa Lundbye L.
AU - Artati, Anna A.
AU - Arumugam, Manimozhiyan
AU - Atabaki-Pasdar, Naeimeh
AU - Baltauss, Tania
AU - Banasik, Karina
AU - Barnett, Anna L.
AU - Baum, Patrick
AU - Bell, Jimmy D.
AU - Beulens, Joline W.
AU - Bianzano, Susanna B.
AU - Bizzotto, Roberto
AU - Bonnefond, Amelie
AU - Cabrelli, Louise
AU - Dale, Matilda
AU - Dawed, Adem Y.
AU - de Preville, Nathalie
AU - Dekkers, Koen F.
AU - Deshmukh, Harshal A.
AU - Dings, Christiane
AU - Donnelly, Louise
AU - Dutta, Avirup
AU - Ehrhardt, Beate
AU - Engelbrechtsen, Line
AU - Eriksen, Rebeca
AU - Fan, Yong
AU - Ferrer, Jorge
AU - Fitipaldi, Hugo
AU - Forman, Annemette
AU - Fritsche, Andreas
AU - Froguel, Philippe
AU - Gassenhuber, Johann
AU - Gough, Stephen
AU - Graefe-Mody, Ulrike
AU - Grempler, Rolf
AU - Groeneveld, Lenka
AU - Groop, Leif
AU - Gudmundsdóttir, Valborg
AU - Gupta, Ramneek
AU - Hennige, Anita M.H.
AU - Hill, Anita V.
AU - Holl, Reinhard W.
AU - Hudson, Michelle
AU - Jacobsen, Ulrik Plesner
AU - Jennison, Christopher
AU - Johansen, Joachim
AU - Jonsson, Anna
AU - Karaderi, Tugce
AU - Kaye, Jane
AU - Kennedy, Gwen
AU - Klintenberg, Maria
AU - Kuulasmaa, Teemu
AU - Lehr, Thorsten
AU - Loftus, Heather
AU - Lundgaard, Agnete Troen T.
AU - Mazzoni, Gianluca
AU - McRobert, Nicky
AU - McVittie, Ian
AU - Nice, Rachel
AU - Nicolay, Claudia
AU - Nijpels, Giel
AU - Palmer, Colin N.
AU - Pedersen, Helle K.
AU - Perry, Mandy H.
AU - Pomares-Millan, Hugo
AU - Prehn, Cornelia P.
AU - Ramisch, Anna
AU - Rasmussen, Simon
AU - Robertson, Neil
AU - Rodriquez, Marianne
AU - Sackett, Peter
AU - Scherer, Nina
AU - Shah, Nisha
AU - Sihinevich, Iryna
AU - Slieker, Roderick C.
AU - Sondertoft, Nadja B.
AU - Steckel-Hamann, Birgit
AU - Thomas, Melissa K.
AU - Thomas, Cecilia Engel E.
AU - Thomas, Elizabeth Louise L.
AU - Thorand, Barbara
AU - Thorne, Claire E.
AU - Tillner, Joachim
AU - Tura, Andrea
AU - Uhlen, Mathias
AU - van Leeuwen, Nienke
AU - van Oort, Sabine
AU - Verkindt, Helene
AU - Vogt, Josef
AU - Wad Sackett, Peter W.
AU - Wesolowska-Andersen, Agata
AU - Whitcher, Brandon
AU - White, Margaret W.
AU - Adamski, Jerzy
AU - Schwenk, Jochen M.
AU - Pearson, Ewan R.
AU - Dermitzakis, Emmanouil T.
AU - Viñuela, Ana
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-40569-3
DO - 10.1038/s41467-023-40569-3
M3 - Journal article
C2 - 37604891
AN - SCOPUS:85168454423
VL - 14
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 5062
ER -