Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21042317
TITLE
Genome-wide association study of major depressive disorder: new results, meta-analysis, and lessons learned.
ABSTRACT
Major depressive disorder (MDD) is a common complex disorder with a partly genetic etiology. We conducted a genome-wide association study of the MDD2000+ sample (2431 cases, 3673 screened controls and >1 M imputed single-nucleotide polymorphisms (SNPs)). No SNPs achieved genome-wide significance either in the MDD2000+ study, or in meta-analysis with two other studies totaling 5763 cases and 6901 controls. These results imply that common variants of intermediate or large effect do not have main effects in the genetic architecture of MDD. Suggestive but notable results were (a) gene-based tests suggesting roles for adenylate cyclase 3 (ADCY3, 2p23.3) and galanin (GAL, 11q13.3); published functional evidence relates both of these to MDD and serotonergic signaling; (b) support for the bipolar disorder risk variant SNP rs1006737 in CACNA1C (P=0.020, odds ratio=1.10); and (c) lack of support for rs2251219, a SNP identified in a meta-analysis of affective disorder studies (P=0.51). We estimate that sample sizes 1.8- to 2.4-fold greater are needed for association studies of MDD compared with those for schizophrenia to detect variants that explain the same proportion of total variance in liability. Larger study cohorts characterized for genetic and environmental risk factors accumulated prospectively are likely to be needed to dissect more fully the etiology of MDD.
DATE PUBLISHED
2012 Jan
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2010/11/02
entrez 2010/11/03 06:00
pubmed 2010/11/03 06:00
medline 2012/05/09 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Wray NR Wray N R NR Genetic Epidemiology, Molecular Epidemiology, Psychiatric Genetics and Queensland Statistical Genetics Laboratories, Queensland Institute of Medical Research, Brisbane, QLD, Australia. naomi.wray@qimr.edu.au
Pergadia ML Pergadia M L ML
Blackwood DH Blackwood D H R DH
Penninx BW Penninx B W J H BW
Gordon SD Gordon S D SD
Nyholt DR Nyholt D R DR
Ripke S Ripke S S
MacIntyre DJ MacIntyre D J DJ
McGhee KA McGhee K A KA
Maclean AW Maclean A W AW
Smit JH Smit J H JH
Hottenga JJ Hottenga J J JJ
Willemsen G Willemsen G G
Middeldorp CM Middeldorp C M CM
de Geus EJ de Geus E J C EJ
Lewis CM Lewis C M CM
McGuffin P McGuffin P P
Hickie IB Hickie I B IB
van den Oord EJ van den Oord E J C G EJ
Liu JZ Liu J Z JZ
Macgregor S Macgregor S S
McEvoy BP McEvoy B P BP
Byrne EM Byrne E M EM
Medland SE Medland S E SE
Statham DJ Statham D J DJ
Henders AK Henders A K AK
Heath AC Heath A C AC
Montgomery GW Montgomery G W GW
Martin NG Martin N G NG
Boomsma DI Boomsma D I DI
Madden PA Madden P A F PA
Sullivan PF Sullivan P F PF
INVESTIGATORS
JOURNAL
VOLUME: 17
ISSUE: 1
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2012
MONTH: Jan
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
DA019951 NIDA NIH HHS United States
DA12854 NIDA NIH HHS United States
G0701420 Medical Research Council United Kingdom
K05 AA017688 NIAAA NIH HHS United States
MH059565 NIMH NIH HHS United States
MH059571 NIMH NIH HHS United States
MH059588 NIMH NIH HHS United States
MH061675 NIMH NIH HHS United States
MH067257 NIMH NIH HHS United States
MH080403 NIMH NIH HHS United States
MH59566 NIMH NIH HHS United States
MH59586 NIMH NIH HHS United States
MH59587 NIMH NIH HHS United States
MH60870 NIMH NIH HHS United States
MH66206 NIMH NIH HHS United States
R01 DA012854 NIDA NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
U01 MH060879 NIMH NIH HHS United States
Chief Scientist Office United Kingdom
Medical Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adenylyl Cyclases genetics
Adolescent genetics
Adult genetics
Calcium Channels, L-Type genetics
Depressive Disorder, Major genetics
Female genetics
Galanin genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study genetics
Genotype genetics
Humans genetics
Male genetics
Middle Aged genetics
Odds Ratio genetics
Polymorphism, Single Nucleotide genetics
Principal Component Analysis genetics
Sex Factors genetics
Young Adult genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 CACNA1C protein, human
0 Calcium Channels, L-Type
88813-36-9 Galanin
EC 4.6.1.1 Adenylyl Cyclases
EC 4.6.1.1 adenylate cyclase 3
OTHER ID's
OTHERID SOURCE
PMC3252611 NLM