Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 203-210 |
| Number of pages | 8 |
| Journal | Brain, Behavior, and Immunity |
| Volume | 67 |
| DOIs | |
| Publication status | Published - Jan 1 2018 |
Bibliographical note
Funding Information:We thank all the participants of the studies for their generous contribution. Funding: This paper represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London . The views expressed are those of the authors and not necessarily those of the National Health Service , the NIHR , or the Department of Health . SC-W was supported by an NIHR Biomedical Research Centre Fellowship at the Institute of Psychiatry, King’s College London, U.K., and Matthew Flinders Fellowship, Flinders University, South Australia, Australia. HLF was supported by an MQ Fellows Award ( MQ14F40 ). CML has received funding from the European Community's Seventh Framework Programme under the Marie Curie Industry-Academia Partnership and Pathways (grant 286213 ). The RADIANT studies were funded by a joint grant from the U.K. Medical Research Council and GlaxoSmithKline ( G0701420 ) and by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King's College London. This report represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The Münster sample was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 to UD; SFB-TRR58, Project C09 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of Münster (grant Dan3/012/17 to UD) and MOODINFLAME FP7-HEALTH-2007-B Nr. 222963 (to VA).
Funding Information:
We thank all the participants of the studies for their generous contribution. Funding: This paper represents independent research supported by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health. SC-W was supported by an NIHR Biomedical Research Centre Fellowship at the Institute of Psychiatry, King's College London, U.K., and Matthew Flinders Fellowship, Flinders University, South Australia, Australia. HLF was supported by an MQ Fellows Award (MQ14F40). CML has received funding from the European Community's Seventh Framework Programme under the Marie Curie Industry-Academia Partnership and Pathways (grant 286213). The RADIANT studies were funded by a joint grant from the U.K. Medical Research Council and GlaxoSmithKline (G0701420) and by the National Institute for Health Research (NIHR) Biomedical Research Centre for Mental Health at South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King's College London. This report represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The M?nster sample was funded by the German Research Foundation (DFG, grant FOR2107 DA1151/5-1 to UD; SFB-TRR58, Project C09 to UD) and the Interdisciplinary Center for Clinical Research (IZKF) of the medical faculty of M?nster (grant Dan3/012/17 to UD) and MOODINFLAME FP7-HEALTH-2007-B Nr. 222963 (to VA).
Publisher Copyright:
© 2017 Elsevier Inc.
ASJC Scopus Subject Areas
- Immunology
- Endocrine and Autonomic Systems
- Behavioral Neuroscience