@misc{10481/63112,
year = {2017},
month = {2},
url = {http://hdl.handle.net/10481/63112},
abstract = {BACKGROUND: 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.},
organization = {United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Mental Health (NIMH)
	
MH085520
MH080403},
organization = {SURFsara},
organization = {Netherlands Scientific Organization 	
NWO 480-05-003},
organization = {Department of Psychology,  Vrije Universiteit Amsterdam},
organization = {Dutch Brain Foundation},
organization = {Federal Ministry of Education & Research (BMBF)
	
01GS08144
01GS08147},
organization = {National Genome Research Network plus, and through the Integrated Network Integrated Understanding of Causes and Mechanisms in Mental Disorders},
organization = {e:Med Programme 	
01ZX1314A
01ZX1314G},
organization = {German Research Foundation (DFG)
	
FOR2107
RI908/11-1
NO246/10-1},
organization = {United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Mental Health (NIMH)
	
MH061686
MH059542
MH075131
MH059552
MH059541
MH060912},
organization = {Federal Ministry of Education & Research (BMBF)
	
01ES0811},
organization = {Bavarian Ministry of Commerce},
organization = {Federal Ministry of Education & Research (BMBF)
	
NGFN2
NGFN-Plus
FKZ 01GS0481
01GS08145},
organization = {Netherlands Organization for Scientific Research (MagW/ZonMW) 	
904-61-090
985-10-002
904-61-193
480-04004
400-05-717
912-100-20},
organization = {Spinozapremie 	
56-464-14192},
organization = {Geestkracht program 	
10-000-1002},
organization = {Center for Medical Systems Biology (NWO Genomics)},
organization = {Biobanking and Biomolecular Resources Research Infrastructure},
organization = {Vrije Universiteit's Institutes for Health and Care Research and Neuroscience Campus Amsterdam},
organization = {BIC/BioAssist/RK 	
2008.024},
organization = {European Science Foundation (ESF)
	
EU/QLRT-200101254},
organization = {European Union (EU)
	
FP7/2007-2013},
organization = {ENGAGE 	
HEALTH-F4-2007-201413},
organization = {European Science Council 	
ERC 230374},
organization = {United States Department of Health & Human Services
National Institutes of Health (NIH) - USA},
organization = {GAIN},
organization = {United States Department of Health & Human Services

National Institutes of Health (NIH) - USA

NIH National Institute of Mental Health (NIMH)
	
MH081802
MH072802
N01MH90003},
organization = {National Health and Medical Research Council of Australia
	
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389892
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organization = {Australian Research Council
	
FT0991360
FT0991022},
organization = {FP-5 GenomEUtwin Project 	
QLG2-CT-2002-01254},
organization = {United States Department of Health & Human Services

National Institutes of Health (NIH) - USA
	
AA07535
AA10248
AA13320
AA13321
AA13326
AA14041
MH66206
DA12854
DA019951
U01 DK066134},
organization = {Center for Inherited Disease Research (Baltimore, MD)},
organization = {UK Medical Research Council and GlaxoSmithKline 	
G0701420},
organization = {National Institute for Health Research (NIHR)},
organization = {Maudsley National Health Service Foundation Trust},
organization = {Institute of Psychiatry, King's College London},
organization = {Medical Research Council UK (MRC)
	
G0000647},
organization = {European Union (EU)
	
286213},
organization = {European Commission Framework 6 grant (EC) 	
LSHB-CT2003- 503428},
organization = {GlaxoSmithKline},
organization = {Faculty of Biology and Medicine of Lausanne},
organization = {Swiss National Science Foundation (SNSF)
	
3200B0-105993
3200B0-118308
33CSCO-122661
33CS30-139468
33CS30-148401},
organization = {GlaxoSmithKline Clinical Genetics},
organization = {Federal Ministry of Education & Research (BMBF)
	
01ZZ9603
01ZZ0103
01ZZ0403
03ZIK012},
organization = {Ministry of Cultural Affairs},
organization = {Social Ministry of the Federal State of Mecklenburg-West Pomerania},
organization = {Siemens Healthcare, Erlangen, Germany},
organization = {German Research Foundation (DFG)
	
GR 1912/5-1
FOR 2107
DA1151/5-1},
organization = {Swedish Ministry for Higher Education},
organization = {Swedish Research Council
	
M-2005-1112},
organization = {GenomEUtwin 	
QLG2-CT-2002-01254
EU/QLRT2001-01254},
organization = {Swedish Foundation for Strategic Research},
organization = {Danske Strategiske Forskningsrad (DSF)},
organization = {Stanley Research Foundation},
organization = {European Union (EU)
	
N Health-F2-2008-222963},
organization = {Innovative Medizinische Forschung of the Medical Faculty of Munster 	
DA120903
DA111107
DA211012},
organization = {Wellcome Trust Strategic Award "Stratifying Resilience and Depression Longitudinally" 	
104036/Z/14/Z},
organization = {Chief Scientist Office of the Scottish Government Health Directorates 	
CZD/16/6},
organization = {Scottish Funding Council 	
HR03006},
organization = {Broad Institute Center for Genotyping and Analysis 	
U54 RR020278},
organization = {NARSAD},
organization = {Biotechnology and Biological Sciences Research Council (BBSRC)},
organization = {Medical Research Council UK (MRC)},
organization = {Federal Ministry of Education & Research (BMBF)},
organization = {Interdisciplinary Center for Clinical Research Munster},
organization = {National Health and Medical Research Council of Australia},
organization = {MRC-BBSRC, Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative 	
MR/K026992/1},
organization = {German Research Foundation (DFG)},
organization = {Federal Ministry of Education},
organization = {Research Germany and speakers honoraria from Eli Lilly and Servier},
organization = {Medical Research Council UK (MRC)},
organization = {Biotechnology and Biological Sciences Research Council (BBSRC)},
organization = {NRS Career Fellowship - Chief Scientist Office},
organization = {Scottish Funding Council Senior Clinical Fellowship},
organization = {Dame Theresa and Mortimer Sackler Foundation},
organization = {Netherlands Organization for Scientific Research (NWO)
	
NOW VENI 916-76-125},
organization = {Lundbeckfonden
	
R155-2014-1724},
organization = {Medical Research Council UK (MRC)
	
MR/K026992/1
MC_PC_U127561128
1292844},
organization = {Chief Scientist Office 	
CZD/16/6/4},
publisher = {Elsevier},
keywords = {Age at onset},
keywords = {Genome-wide association study (GWAS)},
keywords = {Heterogeneity},
keywords = {Major depressive disorder},
keywords = {Polygenic scoring},
keywords = {Stratification},
title = {Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium},
doi = {10.1016/j.biopsych.2016.05.010},
author = {Power, Robert A. and Rivera Sánchez, Margarita and CONVERGE Consortium and CARDIoGRAM Consortium and GERAD1 Consortium},
}