title: Type I interferon signaling genes in recurrent major depression: increased expression detected by whole-blood RNA sequencing.
abstract: A study of genome-wide gene expression in major depressive disorder (MDD) was undertaken in a large population-based sample to determine whether altered expression levels of genes and pathways could provide insights into biological mechanisms that are relevant to this disorder. Gene expression studies have the potential to detect changes that may be because of differences in common or rare genomic sequence variation, environmental factors or their interaction. We recruited a European ancestry sample of 463 individuals with recurrent MDD and 459 controls, obtained self-report and semi-structured interview data about psychiatric and medical history and other environmental variables, sequenced RNA from whole blood and genotyped a genome-wide panel of common single-nucleotide polymorphisms. We used analytical methods to identify MDD-related genes and pathways using all of these sources of information. In analyses of association between MDD and expression levels of 13 857 single autosomal genes, accounting for multiple technical, physiological and environmental covariates, a significant excess of low P-values was observed, but there was no significant single-gene association after genome-wide correction. Pathway-based analyses of expression data detected significant association of MDD with increased expression of genes in the interferon α/β signaling pathway. This finding could not be explained by potentially confounding diseases and medications (including antidepressants) or by computationally estimated proportions of white blood cell types. Although cause-effect relationships cannot be determined from these data, the results support the hypothesis that altered immune signaling has a role in the pathogenesis, manifestation, and/or the persistence and progression of MDD.
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Mostafavi
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Battle
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Psychiatry, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Potash
authors.affiliation: Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Weissman
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
authors.forename: J
authors.initials: J
authors.lastname: Shi
authors.affiliation: Biomedical Genomics Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Beckman
authors.affiliation: Personalis, Inc., Menlo Park, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: Haudenschild
authors.affiliation: Illumina, Inc., La Jolla, CA, USA.
authors.forename: C
authors.initials: C
authors.lastname: McCormick
authors.affiliation: Centrillion Biosciences, Inc., Palo Alto, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Mei
authors.affiliation: Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Gameroff
authors.affiliation: Department of Psychiatry, University of Iowa Hospitals & Clinics, Iowa City, IA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Gindes
authors.affiliation: Department of Psychiatry, Columbia University and New York State Psychiatric Institute, New York, NY, USA.
authors.forename: P
authors.initials: P
authors.lastname: Adams
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: F S
authors.initials: FS
authors.lastname: Goes
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: F M
authors.initials: FM
authors.lastname: Mondimore
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: MacKinnon
authors.affiliation: Depatment of Clinical Psychology, American University, Washington DC, DC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Notes
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: B
authors.initials: B
authors.lastname: Schweizer
authors.affiliation: Department of Microbiology & Immunology, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Furman
authors.affiliation: 1] Department of Genetics, Stanford University, Stanford, CA, USA [2] Department of Pathology, Stanford University, Stanford, CA, USA.
authors.forename: S B
authors.initials: SB
authors.lastname: Montgomery
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: A E
authors.initials: AE
authors.lastname: Urban
authors.affiliation: Department of Computer Science, Stanford University, Stanford, CA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Koller
authors.affiliation: Department of Psychiatry and Behavioral Science, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Levinson
mesh_terms: D000328:Adult; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D055106:Genome-Wide Association Study; D006801:Humans; D007370:Interferon Type I / Q000235:genetics*; D007407:Interviews as Topic; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D057566:Self Report; D017423:Sequence Analysis, RNA / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D007370:Interferon Type I