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 languageEnglish
Article number100457
JournalCell Genomics
Volume3
Issue12
Pages (from-to)100457
ISSN2666-979X
DOIs
Publication statusPublished - 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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