The genetic landscape of neuro-related proteins in human plasma

Linda Repetto; Jiantao Chen; Zhijian Yang; Ranran Zhai; Paul R.H.J. Timmers; Xiao Feng; Ting Li; Yue Yao; Denis Maslov; Anna Timoshchuk; Fengyu Tu; Emma L. Twait; Sebastian May-Wilson; Marisa D. Muckian; Bram P. Prins; Grace Png; Charles Kooperberg; Åsa Johansson; Robert F. Hillary; Eleanor Wheeler; Lu Pan; Yazhou He; Sofia Klasson; Shahzad Ahmad; James E. Peters; Arthur Gilly; Maria Karaleftheri; Emmanouil Tsafantakis; Jeffrey Haessler; Ulf Gyllensten; Sarah E. Harris; Nicholas J. Wareham; Andreas Göteson; Cecilia Lagging; Mohammad Arfan Ikram; Cornelia M. van Duijn; Christina Jern; Mikael Landén; Claudia Langenberg; Ian J. Deary; Riccardo E. Marioni; Stefan Enroth; Alexander P. Reiner; George Dedoussis; Eleftheria Zeggini; Sodbo Sharapov; Yurii S. Aulchenko; Adam S. Butterworth; Anders Mälarstig; James F. Wilson; Pau Navarro; Xia Shen

doi:10.1038/s41562-024-01963-z

The genetic landscape of neuro-related proteins in human plasma

Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul R.H.J. Timmers, Xiao Feng, Ting Li, Yue Yao, Denis Maslov, Anna Timoshchuk, Fengyu Tu, Emma L. Twait, Sebastian May-Wilson, Marisa D. Muckian, Bram P. Prins, Grace Png, Charles Kooperberg, Åsa Johansson, Robert F. Hillary, Eleanor WheelerLu Pan, Yazhou He, Sofia Klasson, Shahzad Ahmad, James E. Peters, Arthur Gilly, Maria Karaleftheri, Emmanouil Tsafantakis, Jeffrey Haessler, Ulf Gyllensten, Sarah E. Harris, Nicholas J. Wareham, Andreas Göteson, Cecilia Lagging, Mohammad Arfan Ikram, Cornelia M. van Duijn, Christina Jern, Mikael Landén, Claudia Langenberg, Ian J. Deary, Riccardo E. Marioni, Stefan Enroth, Alexander P. Reiner, George Dedoussis, Eleftheria Zeggini, Sodbo Sharapov, Yurii S. Aulchenko, Adam S. Butterworth, Anders Mälarstig, James F. Wilson, Pau Navarro, Xia Shen^*

^*Corresponding author for this work

Julius Center, dept. Epidemiology & Health Economics

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

Original language	English
Article number	doi.org/10.1038/s41562-024-01963-z
Pages (from-to)	2222-2234
Number of pages	13
Journal	NATURE HUMAN BEHAVIOUR
Volume	8
Issue number	11
Early online date	29 Aug 2024
DOIs	https://doi.org/10.1038/s41562-024-01963-z
Publication status	Published - Nov 2024

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Repetto, L., Chen, J., Yang, Z., Zhai, R., Timmers, P. R. H. J., Feng, X., Li, T., Yao, Y., Maslov, D., Timoshchuk, A., Tu, F., Twait, E. L., May-Wilson, S., Muckian, M. D., Prins, B. P., Png, G., Kooperberg, C., Johansson, Å., Hillary, R. F., ... Shen, X. (2024). The genetic landscape of neuro-related proteins in human plasma. NATURE HUMAN BEHAVIOUR, 8(11), 2222-2234. Article doi.org/10.1038/s41562-024-01963-z. https://doi.org/10.1038/s41562-024-01963-z

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title = "The genetic landscape of neuro-related proteins in human plasma",

abstract = "Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein{\textquoteright}s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.",

author = "Linda Repetto and Jiantao Chen and Zhijian Yang and Ranran Zhai and Timmers, {Paul R.H.J.} and Xiao Feng and Ting Li and Yue Yao and Denis Maslov and Anna Timoshchuk and Fengyu Tu and Twait, {Emma L.} and Sebastian May-Wilson and Muckian, {Marisa D.} and Prins, {Bram P.} and Grace Png and Charles Kooperberg and {\AA}sa Johansson and Hillary, {Robert F.} and Eleanor Wheeler and Lu Pan and Yazhou He and Sofia Klasson and Shahzad Ahmad and Peters, {James E.} and Arthur Gilly and Maria Karaleftheri and Emmanouil Tsafantakis and Jeffrey Haessler and Ulf Gyllensten and Harris, {Sarah E.} and Wareham, {Nicholas J.} and Andreas G{\"o}teson and Cecilia Lagging and Ikram, {Mohammad Arfan} and {van Duijn}, {Cornelia M.} and Christina Jern and Mikael Land{\'e}n and Claudia Langenberg and Deary, {Ian J.} and Marioni, {Riccardo E.} and Stefan Enroth and Reiner, {Alexander P.} and George Dedoussis and Eleftheria Zeggini and Sodbo Sharapov and Aulchenko, {Yurii S.} and Butterworth, {Adam S.} and Anders M{\"a}larstig and Wilson, {James F.} and Pau Navarro and Xia Shen",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature Limited 2024.",

year = "2024",

month = nov,

doi = "10.1038/s41562-024-01963-z",

language = "English",

volume = "8",

pages = "2222--2234",

number = "11",

}

Repetto, L, Chen, J, Yang, Z, Zhai, R, Timmers, PRHJ, Feng, X, Li, T, Yao, Y, Maslov, D, Timoshchuk, A, Tu, F, Twait, EL, May-Wilson, S, Muckian, MD, Prins, BP, Png, G, Kooperberg, C, Johansson, Å, Hillary, RF, Wheeler, E, Pan, L, He, Y, Klasson, S, Ahmad, S, Peters, JE, Gilly, A, Karaleftheri, M, Tsafantakis, E, Haessler, J, Gyllensten, U, Harris, SE, Wareham, NJ, Göteson, A, Lagging, C, Ikram, MA, van Duijn, CM, Jern, C, Landén, M, Langenberg, C, Deary, IJ, Marioni, RE, Enroth, S, Reiner, AP, Dedoussis, G, Zeggini, E, Sharapov, S, Aulchenko, YS, Butterworth, AS, Mälarstig, A, Wilson, JF, Navarro, P & Shen, X 2024, 'The genetic landscape of neuro-related proteins in human plasma', NATURE HUMAN BEHAVIOUR, vol. 8, no. 11, doi.org/10.1038/s41562-024-01963-z, pp. 2222-2234. https://doi.org/10.1038/s41562-024-01963-z

TY - JOUR

T1 - The genetic landscape of neuro-related proteins in human plasma

AU - Repetto, Linda

AU - Chen, Jiantao

AU - Yang, Zhijian

AU - Zhai, Ranran

AU - Timmers, Paul R.H.J.

AU - Feng, Xiao

AU - Li, Ting

AU - Yao, Yue

AU - Maslov, Denis

AU - Timoshchuk, Anna

AU - Tu, Fengyu

AU - Twait, Emma L.

AU - May-Wilson, Sebastian

AU - Muckian, Marisa D.

AU - Prins, Bram P.

AU - Png, Grace

AU - Kooperberg, Charles

AU - Johansson, Åsa

AU - Hillary, Robert F.

AU - Wheeler, Eleanor

AU - Pan, Lu

AU - He, Yazhou

AU - Klasson, Sofia

AU - Ahmad, Shahzad

AU - Peters, James E.

AU - Gilly, Arthur

AU - Karaleftheri, Maria

AU - Tsafantakis, Emmanouil

AU - Haessler, Jeffrey

AU - Gyllensten, Ulf

AU - Harris, Sarah E.

AU - Wareham, Nicholas J.

AU - Göteson, Andreas

AU - Lagging, Cecilia

AU - Ikram, Mohammad Arfan

AU - van Duijn, Cornelia M.

AU - Jern, Christina

AU - Landén, Mikael

AU - Langenberg, Claudia

AU - Deary, Ian J.

AU - Marioni, Riccardo E.

AU - Enroth, Stefan

AU - Reiner, Alexander P.

AU - Dedoussis, George

AU - Zeggini, Eleftheria

AU - Sharapov, Sodbo

AU - Aulchenko, Yurii S.

AU - Butterworth, Adam S.

AU - Mälarstig, Anders

AU - Wilson, James F.

AU - Navarro, Pau

AU - Shen, Xia

PY - 2024/11

Y1 - 2024/11

N2 - Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

AB - Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioural traits and the disease aetiology of neuropsychiatric disorders. Here the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,000 individuals for 184 neuro-related proteins in human plasma. The analysis identified 125 cis-regulatory protein quantitative trait loci (cis-pQTL) and 164 trans-pQTL. The mapped pQTL capture on average 50% of each protein’s heritability. At the cis-pQTL, multiple proteins shared a genetic basis with human behavioural traits such as alcohol and food intake, smoking and educational attainment, as well as neurological conditions and psychiatric disorders such as pain, neuroticism and schizophrenia. Integrating with established drug information, the causal inference analysis validated 52 out of 66 matched combinations of protein targets and diseases or side effects with available drugs while suggesting hundreds of repurposing and new therapeutic targets.

UR - http://www.scopus.com/inward/record.url?scp=85202605198&partnerID=8YFLogxK

U2 - 10.1038/s41562-024-01963-z

DO - 10.1038/s41562-024-01963-z

M3 - Article

AN - SCOPUS:85202605198

SN - 2397-3374

VL - 8

SP - 2222

EP - 2234

JO - NATURE HUMAN BEHAVIOUR

JF - NATURE HUMAN BEHAVIOUR

IS - 11

M1 - doi.org/10.1038/s41562-024-01963-z

ER -

The genetic landscape of neuro-related proteins in human plasma

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