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

• Published in: Cell genomics 2023-12, Vol.3 (12), p.100457, Article 100457
• Main Authors: Borbye-Lorenzen, Nis, Zhu, Zhihong, Agerbo, Esben, Albiñana, Clara, Benros, Michael E., Bian, Beilei, Børglum, Anders D., Bulik, Cynthia M., Debost, Jean-Christophe Philippe Goldtsche, Grove, Jakob, Hougaard, David M., McRae, Allan F., Mors, Ole, Mortensen, Preben Bo, Musliner, Katherine L., Nordentoft, Merete, Petersen, Liselotte V., Privé, Florian, Sidorenko, Julia, Skogstrand, Kristin, Werge, Thomas, Wray, Naomi R., Vilhjálmsson, Bjarni J., McGrath, John J.
• Format: Article
• Language: English
• Subjects: autoimmune disorders; complement component; dried blood spots; genome-wide association study; Medicin och hälsovetenskap; Mendelian randomization; phenome-wide association study; psychiatric disorders; schizophrenia
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2023.100457

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. [Display omitted] •The genetic correlates of two key complement components (C3, C4) are described•Neonatal C4 concentration was not associated with six mental disorders•Higher concentration of C3 was associated with reduced schizophrenia in women•Mendelian randomization linked C4 concentration and five autoimmune disorders The innate immune system has been linked to schizophrenia and autoimmune disorders. We examined neonatal circulating C3 and C4 protein concentrations in 68,768 neonates and the risk of six mental disorders. We found no associations between C4 concentration and mental disorders, but C3 concentration was associated with a reduced risk of schizophrenia in females. We described the genetic correlates of neonatal circulating C3 and C4. Mendelian randomization linked C4 and an altered risk of five types of autoimmune disorder.