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A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism

Psychiatric disorders and neuroticism are closely associated with central nervous system, whose proper functioning depends on efficient protein renewal. This study aims to systematically analyze the association between anxiety / depression / neuroticism and each of the 439 proteins. 47,536 pQTLs of...

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Autores principales: Cheng, Bolun, Yang, Xuena, Cheng, Shiqiang, Li, Chun’e, Zhang, Huijie, Liu, Li, Meng, Peilin, Jia, Yumeng, Wen, Yan, Zhang, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308259/
https://www.ncbi.nlm.nih.gov/pubmed/35870967
http://dx.doi.org/10.1186/s13041-022-00954-3
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author Cheng, Bolun
Yang, Xuena
Cheng, Shiqiang
Li, Chun’e
Zhang, Huijie
Liu, Li
Meng, Peilin
Jia, Yumeng
Wen, Yan
Zhang, Feng
author_facet Cheng, Bolun
Yang, Xuena
Cheng, Shiqiang
Li, Chun’e
Zhang, Huijie
Liu, Li
Meng, Peilin
Jia, Yumeng
Wen, Yan
Zhang, Feng
author_sort Cheng, Bolun
collection PubMed
description Psychiatric disorders and neuroticism are closely associated with central nervous system, whose proper functioning depends on efficient protein renewal. This study aims to systematically analyze the association between anxiety / depression / neuroticism and each of the 439 proteins. 47,536 pQTLs of 439 proteins in brain, plasma and cerebrospinal fluid (CSF) were collected from recent genome-wide association study. Polygenic risk scores (PRS) of the 439 proteins were then calculated using the UK Biobank cohort, including 120,729 subjects of neuroticism, 255,354 subjects of anxiety and 316,513 subjects of depression. Pearson correlation analyses were performed to evaluate the correlation between each protein and each of the mental traits by using calculated PRSs as the instrumental variables of protein. In general population, six correlations were identified in plasma and CSF such as plasma protease C1 inhibitor (C1-INH) with neuroticism score (r = − 0.011, P = 2.56 × 10(− 9)) in plasma, C1-INH with neuroticism score (r = -0.010, P = 3.09 × 10(− 8)) in CSF, and ERBB1 with self-reported depression (r = − 0.012, P = 4.65 × 10(− 5)) in CSF. C1-INH and ERBB1 may induce neuroticism and depression by affecting brain function and synaptic development. Gender subgroup analyses found that BST1 was correlated with neuroticism score in male CSF (r = − 0.011, P = 1.80 × 10(− 5)), while CNTN2 was correlated with depression score in female brain (r = − 0.013, P = 6.43 × 10(− 4)). BST1 and CNTN2 may be involved in nervous system metabolism and brain health. Six common candidate proteins were associated with all three traits (P < 0.05) and were confirmed in relevant proteomic studies, such as C1-INH in plasma, CNTN2 and MSP in the brain. Our results provide novel clues for revealing the roles of proteins in the development of anxiety, depression and neuroticism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00954-3.
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spelling pubmed-93082592022-07-24 A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism Cheng, Bolun Yang, Xuena Cheng, Shiqiang Li, Chun’e Zhang, Huijie Liu, Li Meng, Peilin Jia, Yumeng Wen, Yan Zhang, Feng Mol Brain Research Psychiatric disorders and neuroticism are closely associated with central nervous system, whose proper functioning depends on efficient protein renewal. This study aims to systematically analyze the association between anxiety / depression / neuroticism and each of the 439 proteins. 47,536 pQTLs of 439 proteins in brain, plasma and cerebrospinal fluid (CSF) were collected from recent genome-wide association study. Polygenic risk scores (PRS) of the 439 proteins were then calculated using the UK Biobank cohort, including 120,729 subjects of neuroticism, 255,354 subjects of anxiety and 316,513 subjects of depression. Pearson correlation analyses were performed to evaluate the correlation between each protein and each of the mental traits by using calculated PRSs as the instrumental variables of protein. In general population, six correlations were identified in plasma and CSF such as plasma protease C1 inhibitor (C1-INH) with neuroticism score (r = − 0.011, P = 2.56 × 10(− 9)) in plasma, C1-INH with neuroticism score (r = -0.010, P = 3.09 × 10(− 8)) in CSF, and ERBB1 with self-reported depression (r = − 0.012, P = 4.65 × 10(− 5)) in CSF. C1-INH and ERBB1 may induce neuroticism and depression by affecting brain function and synaptic development. Gender subgroup analyses found that BST1 was correlated with neuroticism score in male CSF (r = − 0.011, P = 1.80 × 10(− 5)), while CNTN2 was correlated with depression score in female brain (r = − 0.013, P = 6.43 × 10(− 4)). BST1 and CNTN2 may be involved in nervous system metabolism and brain health. Six common candidate proteins were associated with all three traits (P < 0.05) and were confirmed in relevant proteomic studies, such as C1-INH in plasma, CNTN2 and MSP in the brain. Our results provide novel clues for revealing the roles of proteins in the development of anxiety, depression and neuroticism. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13041-022-00954-3. BioMed Central 2022-07-23 /pmc/articles/PMC9308259/ /pubmed/35870967 http://dx.doi.org/10.1186/s13041-022-00954-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cheng, Bolun
Yang, Xuena
Cheng, Shiqiang
Li, Chun’e
Zhang, Huijie
Liu, Li
Meng, Peilin
Jia, Yumeng
Wen, Yan
Zhang, Feng
A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title_full A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title_fullStr A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title_full_unstemmed A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title_short A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
title_sort large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308259/
https://www.ncbi.nlm.nih.gov/pubmed/35870967
http://dx.doi.org/10.1186/s13041-022-00954-3
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