Volume 67, January 2018, Pages 203-210
aSchool of Psychology, Faculty of Social and Behavioural Sciences, Flinders University, Adelaide, SA, Australia
bFlinders Centre for Innovation in Cancer, School of Medicine, Flinders University, PO Box 2100, Adelaide, SA 5001, Australia
cMRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
dDepartment of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge, UK
eDepartment of Psychology, Goldsmiths, University of London, London, UK
fCentre for Psychiatry, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
gMRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK
hDepartment of Psychiatry, University of Münster, Münster, Germany
iDiscipline of Psychiatry, School of Medicine, The University of Adelaide, Adelaide, SA, Australia
jDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada
Received 24 April 2017, Revised 1 August 2017, Accepted 30 August 2017, Available online 1 September 2017.
•Gene-environment study focusing on comprehensive analysis of immune candidate genes.
•Interaction with childhood maltreatment in predicting recurrent depression.
•Loci identified in the discovery sample taken forward to an independent replication sample.
•Two loci present some evidence for replication in IL-6 and CRP.
•These loci should be targeted for replication in further studies internationally in the future.
Major depressive disorder (MDD) is a prevalent disorder with moderate heritability. Both MDD and interpersonal adversity, including childhood maltreatment, have been consistently associated with elevated inflammatory markers. We investigated interaction between exposure to childhood maltreatment and extensive genetic variation within the inflammation pathway (CRP, IL1b, IL-6, IL11, TNF, TNFR1, and TNFR2) in relation to depression diagnosis. The discovery RADIANT sample included 262 cases with recurrent DSM-IV/ICD-10 MDD, and 288 unaffected controls. The replication Münster cohort included 277 cases with DSM-IV MDD, and 316 unaffected controls. We identified twenty-five single nucleotide polymorphisms (SNPs) following multiple testing correction that interacted with childhood maltreatment to predict depression in the discovery cohort. Seven SNPs representing independent signals (rs1818879, rs1041981, rs4149576, rs616645, rs17882988, rs1061622, and rs3093077) were taken forward for replication. Meta-analyses of the two samples presented evidence for interaction with rs1818879 (IL6) (RD = 0.059, SE = 0.016, p < 0.001), with the replication Münster sample approaching statistical significance in analyses restricted to recurrent MDD and controls following correction for multiple testing (q = 0.066). The CRP locus (rs3093077) showed a similar level of evidence for interaction in the meta-analysis (RD = 0.092, SE = 0.029, p = 0.002), but less compelling evidence in the replication sample alone (recurrent MDD q = 0.198; all MDD q = 0.126). Here we present evidence suggestive of interaction with childhood maltreatment for novel loci in IL-6 (rs1818879) and CRP (rs3093077), increasing risk of depression. Replication is needed by independent groups, targeting these specific variants and interaction with childhood maltreatment on depression risk.