Genetic mechanisms of 184 neuro-related proteins in human plasma

Linda Repetto; Jiantao Chen; Zhijian Yang; Ranran Zhai; Paul R H J Timmers; Ting Li; 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; Adam S Butterworth; Anders Mälarstig; James F Wilson; Pau Navarro; Xia Shen

doi:https://doi.org/10.1101/2023.02.10.23285650

Genetic mechanisms of 184 neuro-related proteins in human plasma

Linda Repetto, Jiantao Chen, Zhijian Yang, Ranran Zhai, Paul R H J Timmers, Ting Li, 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 PetersArthur 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, Adam S Butterworth, Anders Mälarstig, James F Wilson, Pau Navarro, Xia Shen

Research output: Contribution to journal › Article › Academic

Abstract

Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.

Original language	English
Journal	MedRxIv
DOIs	https://doi.org/10.1101/2023.02.10.23285650
Publication status	Published - 14 Feb 2023

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https://doi.org/10.1101/2023.02.10.23285650

Cite this

Repetto, L., Chen, J., Yang, Z., Zhai, R., Timmers, P. R. H. J., Li, T., Twait, E. L., May-Wilson, S., Muckian, M. D., Prins, B. P., Png, G., Kooperberg, C., Johansson, Å., Hillary, R. F., Wheeler, E., Pan, L., He, Y., Klasson, S., Ahmad, S., ... Shen, X. (2023). Genetic mechanisms of 184 neuro-related proteins in human plasma. MedRxIv. https://doi.org/10.1101/2023.02.10.23285650

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title = "Genetic mechanisms of 184 neuro-related proteins in human plasma",

abstract = "Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.",

author = "Linda Repetto and Jiantao Chen and Zhijian Yang and Ranran Zhai and Timmers, {Paul R H J} and Ting Li 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 Butterworth, {Adam S} and Anders M{\"a}larstig and Wilson, {James F} and Pau Navarro and Xia Shen",

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Repetto, L, Chen, J, Yang, Z, Zhai, R, Timmers, PRHJ, Li, T, 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, Butterworth, AS, Mälarstig, A, Wilson, JF, Navarro, P & Shen, X 2023, 'Genetic mechanisms of 184 neuro-related proteins in human plasma', MedRxIv. https://doi.org/10.1101/2023.02.10.23285650

TY - JOUR

T1 - Genetic mechanisms of 184 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 - Li, Ting

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 - Butterworth, Adam S

AU - Mälarstig, Anders

AU - Wilson, James F

AU - Navarro, Pau

AU - Shen, Xia

PY - 2023/2/14

Y1 - 2023/2/14

N2 - Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.

AB - Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-reiated proteins in human plasma. The analysis identified 117 cis-regulatory protein quantitative trait loci (cis-pQTL) and 166 trans-pQTL. The mapped pQTL capture on average 50% of each protein's heritability. Mendelian randomization analyses revealed multiple proteins showing potential causal effects on neuro-reiated traits as well as complex diseases such as hypertension, high cholesterol, immune-related disorders, and psychiatric disorders. Integrating with established drug information, we validated 13 combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets for diseases and comorbidities. This consortium effort provides a large-scale proteogenomic resource for biomedical research.

U2 - https://doi.org/10.1101/2023.02.10.23285650

DO - https://doi.org/10.1101/2023.02.10.23285650

M3 - Article

C2 - 36824751

JO - MedRxIv

JF - MedRxIv

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