Genome-wide association for major depression through age at onset stratification
Power, Robert A., Tansey, Katherine E., Buttenschøn, Henriette Nørmølle, Cohen-Woods, Sarah, Bigdeli, Tim, Hall, Lynsey S., Kutalik, Zoltán, Lee, S. Hong, 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, Dannlowski, Udo, Deary, Ian J., Degenhardt, Franziska, Forstner, Andreas J., Gordon, Scott D., Grabe, Hans J., Grove, Jakob, Hamilton, Steven P., Hayward, Caroline, Heath, Andrew C., Hocking, Lynne J., Homuth, Georg, Hottenga, Jouke J., Kloiber, Stefan, Krogh, Jesper, Landén, Mikael, Lang, Maren, Levinson, Douglas F., Lichtenstein, Paul, Lucae, Susanne, MacIntyre, Donald J., Madden, Pamela, Magnusson, Patrik K.E., Martin, Nicholas G., McIntosh, Andrew 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., consortium, CONVERGE, Consortium, CARDIoGRAM, Consortium, GERAD, Breen, Gerome, & Lewis, Cathryn M. (2016) Genome-wide association for major depression through age at onset stratification. Biological Psychiatry. (In Press)
Major depressive disorder (MDD) is a disabling mood disorder and, despite a known heritable component, a large meta-analysis of GWAS revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age-at-onset (AAO) in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by AAO. Method
Discovery case-control GWASs were performed where cases were stratified using increasing/decreasing AAO-cutoffs; significant SNPs were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 controls for sub-setting. Polygenic score analysis was used to examine if differences in shared genetic risk exists between earlier and adult onset MDD with commonly co-morbid disorders of schizophrenia, bipolar disorder, Alzheimer’s disease, and coronary artery disease. Results
We identify one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, OR=1.16, 95%CI=1.11-1.21, p=5.2x10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset. 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. Keywords
Major Depressive Disorder; GWAS; Age at Onset; Polygenic Scoring; heterogeneity; stratification
Impact and interest:
Citation counts are sourced monthly from and citation databases.
These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.
Citations counts from theindexing service can be viewed at the linked Google Scholar™ search.
Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.
|Item Type:||Journal Article|
|Divisions:||Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
|Copyright Statement:||Under a Creative Commons Attribution Licence|
|Deposited On:||03 Aug 2016 06:05|
|Last Modified:||07 Aug 2016 04:20|
Repository Staff Only: item control page