Power, Robert A

Tansey, Katherine E

Buttenschon, Henriette Normolle

Cohen-Woods, Sarah

Bigdeli, Tim

Hall, Lynsey S

Kutalik, Zoltn

Lee, Sang Hong

Ripke, Stephan

Steinberg, Stacy

Teumer, Alexander

Viktorin, Alexander

Wray, Naomi R

Arolt, Volker

Baune, Bernard T

Boomsma, Dorret I

Borglum, Anders D

Byrne, Enda M

Castelao, Enrique

Craddock, Nick

Craig, Ian W

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

Landen, 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

Muller-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

Breen, Gerome

Lewis, Cathryn M

2017-02-15

<p><b>BACKGROUND:</b> 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. <br/><b>METHODS:</b> 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.</br><br/><b>RESULTS:</b> 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, <i>p</i> = 5.2 × 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.</br><br/><b>CONCLUSIONS:</b> 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.</br></p>

Biological Psychiatry, 81(4), p. 325-335

1873-2402

0006-3223

27519822

https://hdl.handle.net/1959.11/51750

en

Elsevier Inc

Attribution 4.0 International

Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

Journal Article

Publication