Psychology - Collected Works
Permanent URI for this collection
Browsing Psychology - Collected Works by Author "Arolt, Volker"
Now showing 1 - 2 of 2
Results Per Page
ItemGenome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium(Elsevier, 2017-02-15) Power, Robert A ; Tansey, Katherine E ; Buttenschon, Henriette Nørmølle ; Cohen-Woods, Sarah ; Bigdeli, Tim ; Hall, Lynsey S ; Kutalik, Zoltán ; Hong Lee, S ; Ripke, Stephan ; Steinberg, Stacy ; Teumer, Alexander ; Viktorin, Alexander ; Wray, Naomi R ; Arolt, Volker ; Baune, Bernard T ; Boomsma, Dorret I ; Børglum, Anders D ; Byrne, Enda M ; Castelao, Enrique ; Craddock, Nick ; Craig, Ian W ; Dannlowski, Udo ; Deary, Jennifer ; Degenhardt, Franziska ; Forstner, Andreas J ; Gordon, Scott D ; Grabe, Hans J ; Grove, Jakob ; Hamilton, Steven P ; Hayward, Caroline ; Heath, CarolineC ; Hocking, Lynne J ; Homuth, Georg ; Hottenga, Jouke J ; Kloiber, Stefan ; Krogh, Jesper ; Landén, M ; Lang, Maren ; Levinson, Douglas F ; Lichtenstein, Paul ; Lucae, Susanne ; MacIntyre, Donald J ; Madden, Pamela ; Magnusson, Patrik K E ; Martin, Nicholas G ; McIntosh, Anthony M ; Middeldorp, Christel M ; Milaneschi, Yuri ; Montgomery, Grant W ; Mors, Ole ; Müller-Myhsok, Bertram ; Nyholt, Dale R ; Oskarsson, Hogni ; Owen, Michael J ; Padmanabhan, Sandosh ; Penninx, Brenda W J H ; Pergadia, Michele L ; Porteous, David J ; Potash, James B ; Preisig, Martin ; Rivera, Margarita ; Shi, Jianxin ; Shyn, Stanley I ; Sigurdsson, Engilbert ; Smit, Johannes H ; Smith, Blair H ; Stefansson, Hreinn ; Stefansson, Kari ; Strohmaier, Jana ; Sullivan, Patrick F ; Thomson, Pippa ; Thorgeirsson, Thorgeir E ; Van der Auwera, Sandra ; Weissman, Myrna M ; CONVERGE Consortium ; CARDIoGRAM Consortium ; GERAD1 Consortium ; Breen, Gerome ; Lewis, Cathryn MBACKGROUND: Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset. METHODS: Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. RESULTS: We identified one replicated genome-wide significant locus associated with adult-onset (.27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11–1.21, p 5 5.2 3 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD. CONCLUSIONS: We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.
ItemInteraction between childhood maltreatment on immunogenetic risk in depression: Discovery and replication in clinical case-control samples(Elsevier, 2017-09-01) Cohen-Woods, Sarah ; Fisher, Helen L ; Ahmetspahic, Diana ; Douroudis, Konstantinos ; Stacey, David ; Hosang, Georgina ; Korszun, Ania ; Owen, Michael J ; Craddock, Nick ; Arolt, Volker ; Dannlowski, Udo ; Breen, Gerome ; Craig, Ian W ; Farmer, Anne E ; Baune, Bernard T ; Lewis, Cathryn M ; Uher, Rudolf ; McGuffin, Peter WMajor 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.