Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders

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/10.21203/rs.3.rs-2720355/v1

Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders

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 molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related 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-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.

Original language	English
Journal	Research square
DOIs	https://doi.org/10.21203/rs.3.rs-2720355/v1
Publication status	Published - 31 Mar 2023

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https://doi.org/10.21203/rs.3.rs-2720355/v1

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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). Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders. Research square. https://doi.org/10.21203/rs.3.rs-2720355/v1

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title = "Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders",

abstract = "Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related 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-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.",

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, 'Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders', Research square. https://doi.org/10.21203/rs.3.rs-2720355/v1

TY - JOUR

T1 - Unraveling Neuro-Proteogenomic Landscape and Therapeutic Implications for Human Behaviors and Psychiatric Disorders

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 - 2023/3/31

Y1 - 2023/3/31

N2 - Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related 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-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.

AB - Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related 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-related traits such as sleeping, smoking, feelings, alcohol intake, mental health, and psychiatric disorders. Integrating with established drug information, we validated 13 out of 13 matched combinations of protein targets and diseases or side effects with available drugs, while suggesting hundreds of re-purposing and new therapeutic targets. This consortium effort provides a large-scale proteogenomic resource for biomedical research on human behaviors and other neuro-related phenotypes.

U2 - https://doi.org/10.21203/rs.3.rs-2720355/v1

DO - https://doi.org/10.21203/rs.3.rs-2720355/v1

M3 - Article

C2 - 37034613

JO - Research square

JF - Research square

ER -