The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders

Nis Borbye-Lorenzen; Zhihong Zhu; Esben Agerbo; Clara Albiñana; Michael E Benros; Beilei Bian; Anders D Børglum; Cynthia M Bulik; Jean-Christophe Philippe Goldtsche Debost; Jakob Grove; David M Hougaard; Allan F McRae; Ole Mors; Preben Bo Mortensen; Katherine L Musliner; Merete Nordentoft; Liselotte V Petersen; Florian Privé; Julia Sidorenko; Kristin Skogstrand; Thomas Werge; Naomi R Wray; Bjarni J Vilhjálmsson; John J McGrath

doi:10.1016/j.xgen.2023.100457

The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders

Nis Borbye-Lorenzen, Zhihong Zhu, Esben Agerbo, Clara Albiñana, Michael E Benros, Beilei Bian, Anders D Børglum, Cynthia M Bulik, Jean-Christophe Philippe Goldtsche Debost, Jakob Grove, David M Hougaard, Allan F McRae, Ole Mors, Preben Bo Mortensen, Katherine L Musliner, Merete Nordentoft, Liselotte V Petersen, Florian Privé, Julia Sidorenko, Kristin SkogstrandThomas Werge, Naomi R Wray, Bjarni J Vilhjálmsson, John J McGrath

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Abstract

Complement components have been linked to schizophrenia and autoimmune disorders. We examined the association between neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We completed genome-wide association studies (GWASs) for C3 and C4 and applied the summary statistics in Mendelian randomization and phenome-wide association studies related to mental and autoimmune disorders. The GWASs for C3 and C4 protein concentrations identified 15 and 36 independent loci, respectively. We found no associations between neonatal C3 and C4 concentrations and mental disorders in the total sample (both sexes combined); however, post-hoc analyses found that a higher C3 concentration was associated with a reduced risk of schizophrenia in females. Mendelian randomization based on C4 summary statistics found an altered risk of five types of autoimmune disorders. Our study adds to our understanding of the associations between C3 and C4 concentrations and subsequent mental and autoimmune disorders.

Original language	English
Article number	100457
Journal	Cell Genomics
Volume	3
Issue	12
Pages (from-to)	100457
ISSN	2666-979X
DOIs	https://doi.org/10.1016/j.xgen.2023.100457
Publication status	Published - 13 Dec 2023

Keywords

C3
C4
Mendelian randomization
autoimmune disorders
complement component
dried blood spots
genome-wide association study
phenome-wide association study
psychiatric disorders
schizophrenia

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Borbye-Lorenzen, N., Zhu, Z., Agerbo, E., Albiñana, C., Benros, M. E., Bian, B., Børglum, A. D., Bulik, C. M., Debost, J.-C. P. G., Grove, J., Hougaard, D. M., McRae, A. F., Mors, O., Mortensen, P. B., Musliner, K. L., Nordentoft, M., Petersen, L. V., Privé, F., Sidorenko, J., ... McGrath, J. J. (2023). The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders. Cell Genomics, 3(12), 100457. Article 100457. https://doi.org/10.1016/j.xgen.2023.100457

@article{7aa3292aa1a84780bbe1cc4eb7867193,

title = "The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders",

abstract = "Complement components have been linked to schizophrenia and autoimmune disorders. We examined the association between neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We completed genome-wide association studies (GWASs) for C3 and C4 and applied the summary statistics in Mendelian randomization and phenome-wide association studies related to mental and autoimmune disorders. The GWASs for C3 and C4 protein concentrations identified 15 and 36 independent loci, respectively. We found no associations between neonatal C3 and C4 concentrations and mental disorders in the total sample (both sexes combined); however, post-hoc analyses found that a higher C3 concentration was associated with a reduced risk of schizophrenia in females. Mendelian randomization based on C4 summary statistics found an altered risk of five types of autoimmune disorders. Our study adds to our understanding of the associations between C3 and C4 concentrations and subsequent mental and autoimmune disorders.",

keywords = "C3, C4, Mendelian randomization, autoimmune disorders, complement component, dried blood spots, genome-wide association study, phenome-wide association study, psychiatric disorders, schizophrenia",

author = "Nis Borbye-Lorenzen and Zhihong Zhu and Esben Agerbo and Clara Albi{\~n}ana and Benros, {Michael E} and Beilei Bian and B{\o}rglum, {Anders D} and Bulik, {Cynthia M} and Debost, {Jean-Christophe Philippe Goldtsche} and Jakob Grove and Hougaard, {David M} and McRae, {Allan F} and Ole Mors and Mortensen, {Preben Bo} and Musliner, {Katherine L} and Merete Nordentoft and Petersen, {Liselotte V} and Florian Priv{\'e} and Julia Sidorenko and Kristin Skogstrand and Thomas Werge and Wray, {Naomi R} and Vilhj{\'a}lmsson, {Bjarni J} and McGrath, {John J}",

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year = "2023",

month = dec,

day = "13",

doi = "10.1016/j.xgen.2023.100457",

language = "English",

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Borbye-Lorenzen, N, Zhu, Z , Agerbo, E , Albiñana, C, Benros, ME, Bian, B, Børglum, AD, Bulik, CM, Debost, J-CPG , Grove, J, Hougaard, DM, McRae, AF, Mors, O , Mortensen, PB , Musliner, KL, Nordentoft, M, Petersen, LV , Privé, F, Sidorenko, J, Skogstrand, K, Werge, T, Wray, NR, Vilhjálmsson, BJ & McGrath, JJ 2023, 'The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders', Cell Genomics, vol. 3, no. 12, 100457, pp. 100457. https://doi.org/10.1016/j.xgen.2023.100457

The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders. / Borbye-Lorenzen, Nis; Zhu, Zhihong ; Agerbo, Esben et al.
In: Cell Genomics, Vol. 3, No. 12, 100457, 13.12.2023, p. 100457.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders

AU - Borbye-Lorenzen, Nis

AU - Zhu, Zhihong

AU - Agerbo, Esben

AU - Albiñana, Clara

AU - Benros, Michael E

AU - Bian, Beilei

AU - Børglum, Anders D

AU - Bulik, Cynthia M

AU - Debost, Jean-Christophe Philippe Goldtsche

AU - Grove, Jakob

AU - Hougaard, David M

AU - McRae, Allan F

AU - Mors, Ole

AU - Mortensen, Preben Bo

AU - Musliner, Katherine L

AU - Nordentoft, Merete

AU - Petersen, Liselotte V

AU - Privé, Florian

AU - Sidorenko, Julia

AU - Skogstrand, Kristin

AU - Werge, Thomas

AU - Wray, Naomi R

AU - Vilhjálmsson, Bjarni J

AU - McGrath, John J

PY - 2023/12/13

Y1 - 2023/12/13

N2 - Complement components have been linked to schizophrenia and autoimmune disorders. We examined the association between neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We completed genome-wide association studies (GWASs) for C3 and C4 and applied the summary statistics in Mendelian randomization and phenome-wide association studies related to mental and autoimmune disorders. The GWASs for C3 and C4 protein concentrations identified 15 and 36 independent loci, respectively. We found no associations between neonatal C3 and C4 concentrations and mental disorders in the total sample (both sexes combined); however, post-hoc analyses found that a higher C3 concentration was associated with a reduced risk of schizophrenia in females. Mendelian randomization based on C4 summary statistics found an altered risk of five types of autoimmune disorders. Our study adds to our understanding of the associations between C3 and C4 concentrations and subsequent mental and autoimmune disorders.

AB - Complement components have been linked to schizophrenia and autoimmune disorders. We examined the association between neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We completed genome-wide association studies (GWASs) for C3 and C4 and applied the summary statistics in Mendelian randomization and phenome-wide association studies related to mental and autoimmune disorders. The GWASs for C3 and C4 protein concentrations identified 15 and 36 independent loci, respectively. We found no associations between neonatal C3 and C4 concentrations and mental disorders in the total sample (both sexes combined); however, post-hoc analyses found that a higher C3 concentration was associated with a reduced risk of schizophrenia in females. Mendelian randomization based on C4 summary statistics found an altered risk of five types of autoimmune disorders. Our study adds to our understanding of the associations between C3 and C4 concentrations and subsequent mental and autoimmune disorders.

KW - C3

KW - C4

KW - Mendelian randomization

KW - autoimmune disorders

KW - complement component

KW - dried blood spots

KW - genome-wide association study

KW - phenome-wide association study

KW - psychiatric disorders

KW - schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=85179497801&partnerID=8YFLogxK

U2 - 10.1016/j.xgen.2023.100457

DO - 10.1016/j.xgen.2023.100457

M3 - Journal article

C2 - 38116117

SN - 2666-979X

VL - 3

SP - 100457

JO - Cell Genomics

JF - Cell Genomics

IS - 12

M1 - 100457

ER -

The correlates of neonatal complement component 3 and 4 protein concentrations with a focus on psychiatric and autoimmune disorders

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