TY - JOUR
T1 - Alterations observed in the interferon α and β signaling pathway in MDD patients are marginally influenced by cis-acting alleles
AU - Magri, Chiara
AU - Giacopuzzi, Edoardo
AU - Sacco, Chiara
AU - Bocchio-Chiavetto, Luisella
AU - Minelli, Alessandra
AU - Gennarelli, Massimo
N1 - Funding Information:
Data was provided by Dr. Douglas F. Levinson. We gratefully acknowledge the resources were supported by National Institutes of Health/National Institute of Mental Health Grants 5RC2MH089916 (PI: Douglas F. Lev-inson, M.D.; Co-investigators: Myrna M. Weissman, Ph.D., James B. Potash, M.D., MPH, Daphne Koller, Ph.D., and Alexander E. Urban, Ph.D.) and 3R01MH090941 (Co-investigator: Daphne Koller, Ph.D.). This research was supported by grants from the Italian Ministry of Health (Ricerca Corrente).
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/12
Y1 - 2021/12
N2 - Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway.
AB - Major depressive disorder (MDD) is a common psychiatric disorder with a multifactorial aetiology determined by the interaction between genetic and environmental risk factors. Pieces of evidence indicate that inflammation and immune activation may contribute to the onset of MDD playing a role in the pathogenetic mechanism. To date, it is not known to which extent the association between MDD and inflammation is shaped by the genetic background or by the presence of environmental factors. To clarify this issue, we analyzed genotype and blood RNA profiles of 463 MDD cases and 459 controls (NIMH-Study 88/Site621) estimating the Genetic and Environmental Regulated eXpression component of gene expression (GReX and EReX respectively). Both components were tested for association with MDD. Many genes belonging to the α/β interferon signaling pathway showed an association between MDD and EReX, only two between MDD and GReX. Also other MDD differentially expressed genes were more influenced by the EReX than by GReX. These results suggest that impact of the genetic background on MDD blood gene expression alterations is much lower than the contribution of environmental factors and almost absent for the genes of the interferon pathway.
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U2 - 10.1038/s41598-020-80374-2
DO - 10.1038/s41598-020-80374-2
M3 - Article
AN - SCOPUS:85099352130
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 727
ER -