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.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
19065144
TITLE
Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo.
ABSTRACT
Major depressive disorder (MDD) is a common complex trait with enormous public health significance. As part of the Genetic Association Information Network initiative of the US Foundation for the National Institutes of Health, we conducted a genome-wide association study of 435 291 single nucleotide polymorphisms (SNPs) genotyped in 1738 MDD cases and 1802 controls selected to be at low liability for MDD. Of the top 200, 11 signals localized to a 167 kb region overlapping the gene piccolo (PCLO, whose protein product localizes to the cytomatrix of the presynaptic active zone and is important in monoaminergic neurotransmission in the brain) with P-values of 7.7 x 10(-7) for rs2715148 and 1.2 x 10(-6) for rs2522833. We undertook replication of SNPs in this region in five independent samples (6079 MDD independent cases and 5893 controls) but no SNP exceeded the replication significance threshold when all replication samples were analyzed together. However, there was heterogeneity in the replication samples, and secondary analysis of the original sample with the sample of greatest similarity yielded P=6.4 x 10(-8) for the nonsynonymous SNP rs2522833 that gives rise to a serine to alanine substitution near a C2 calcium-binding domain of the PCLO protein. With the integrated replication effort, we present a specific hypothesis for further studies.
DATE PUBLISHED
2009 Apr
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2008/12/09
pubmed 2008/12/10 09:00
medline 2009/08/06 09:00
entrez 2008/12/10 09:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Sullivan PF Sullivan P F PF Department of Genetics, University of North Carolina, Chapel Hill, NC 27599-7264, USA. pfsulliv@med.unc.edu
de Geus EJ de Geus E J C EJ
Willemsen G Willemsen G G
James MR James M R MR
Smit JH Smit J H JH
Zandbelt T Zandbelt T T
Arolt V Arolt V V
Baune BT Baune B T BT
Blackwood D Blackwood D D
Cichon S Cichon S S
Coventry WL Coventry W L WL
Domschke K Domschke K K
Farmer A Farmer A A
Fava M Fava M M
Gordon SD Gordon S D SD
He Q He Q Q
Heath AC Heath A C AC
Heutink P Heutink P P
Holsboer F Holsboer F F
Hoogendijk WJ Hoogendijk W J WJ
Hottenga JJ Hottenga J J JJ
Hu Y Hu Y Y
Kohli M Kohli M M
Lin D Lin D D
Lucae S Lucae S S
Macintyre DJ Macintyre D J DJ
Maier W Maier W W
McGhee KA McGhee K A KA
McGuffin P McGuffin P P
Montgomery GW Montgomery G W GW
Muir WJ Muir W J WJ
Nolen WA Nolen W A WA
Nöthen MM Nöthen M M MM
Perlis RH Perlis R H RH
Pirlo K Pirlo K K
Posthuma D Posthuma D D
Rietschel M Rietschel M M
Rizzu P Rizzu P P
Schosser A Schosser A A
Smit AB Smit A B AB
Smoller JW Smoller J W JW
Tzeng JY Tzeng J-Y JY
van Dyck R van Dyck R R
Verhage M Verhage M M
Zitman FG Zitman F G FG
Martin NG Martin N G NG
Wray NR Wray N R NR
Boomsma DI Boomsma D I DI
Penninx BW Penninx B W J H BW
INVESTIGATORS
JOURNAL
VOLUME: 14
ISSUE: 4
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2009
MONTH: Apr
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
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Hum Mol Genet. 2007 Jan 1;16(1):24-35 17158188
Cites Twin Res Hum Genet. 2006 Dec;9(6):849-57 17254420
Cites Am J Hum Genet. 2007 Apr;80(4):605-15 17357068
Cites Science. 2007 Jun 1;316(5829):1331-6 17463246
Cites Science. 2007 Jun 1;316(5829):1341-5 17463248
Cites Nature. 2007 Jun 7;447(7145):655-60 17554299
Cites Nature. 2007 Jun 7;447(7145):661-78 17554300
Cites Nat Genet. 2007 Jul;39(7):813-5 17597768
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Nat Rev Genet. 2007 Sep;8(9):657-62 17703236
Cites Nat Genet. 2007 Sep;39(9):1045-51 17728769
Cites Nat Genet. 2007 Oct;39(10):1181-6 17898773
Cites Hum Mol Genet. 2007 Oct 15;16 Spec No. 2:R168-73 17911159
Cites Nature. 2007 Oct 18;449(7164):851-61 17943122
Cites Nature. 2007 Oct 18;449(7164):913-8 17943131
Cites Genome Res. 2007 Nov;17(11):1665-74 17921354
Cites Genet Epidemiol. 2007 Dec;31(8):803-12 17549762
Cites Handb Exp Pharmacol. 2008;(184):1-21 18064409
Cites Mol Psychiatry. 2008 Feb;13(2):197-207 17486107
Cites Am J Hum Genet. 2008 Feb;82(2):444-52 18252224
Cites N Engl J Med. 2008 Feb 14;358(7):667-75 18184952
Cites Eur J Hum Genet. 2008 Mar;16(3):335-42 18197199
Cites Science. 2008 Apr 25;320(5875):539-43 18369103
Cites Nat Genet. 2008 May;40(5):638-45 18372903
Cites Am J Hum Genet. 2008 May;82(5):1064-74 18423522
Cites Mol Psychiatry. 2008 Jun;13(6):570-84 18347602
Cites Am J Med Genet B Neuropsychiatr Genet. 2008 Sep 5;147B(6):671-5 18548508
Cites Arch Gen Psychiatry. 2008 Sep;65(9):1062-71 18762592
Cites Int J Methods Psychiatr Res. 2008;17(3):121-40 18763692
Cites Mol Psychiatry. 2009 Jan;14(1):10-7 19002139
Cites Nat Genet. 2008 Sep;40(9):1053-5 18677311
Cites Nat Genet. 2008 Sep;40(9):1056-8 18711365
Cites Biometrics. 1946 Jun;2(3):47-53 21001024
Cites J Clin Epidemiol. 2000 Apr;53(4):351-7 10785565
Cites Am J Psychiatry. 2000 Oct;157(10):1552-62 11007705
Cites EMBO J. 2001 Apr 2;20(7):1605-19 11285225
Cites Biometrics. 1999 Dec;55(4):997-1004 11315092
Cites Twin Res. 2000 Dec;3(4):323-34 11463154
Cites Neuron. 2001 Oct 11;32(1):63-77 11604139
Cites Stat Med. 2002 Jan 15;21(1):35-50 11782049
Cites Am J Epidemiol. 2002 Mar 1;155(5):478-84 11867360
Cites Arch Gen Psychiatry. 2003 Feb;60(2):184-9 12578436
Cites Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):98-101 12707945
Cites Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):118-30 12707949
Cites Genetics. 2003 Jun;164(2):829-33 12807801
Cites JAMA. 2003 Jun 18;289(23):3095-105 12813115
Cites Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5 12883005
Cites Trends Genet. 2003 Oct;19(10):537-42 14550627
Cites Am J Hum Genet. 2004 Jan;74(1):106-20 14681826
Cites Nat Struct Mol Biol. 2004 Jan;11(1):45-53 14718922
Cites Biometrics. 2003 Dec;59(4):1071-81 14969487
Cites Hum Mol Genet. 2004 Apr 1;13 Spec No 1:R57-64 14764619
Cites Genetics. 2004 Jan;166(1):611-9 15020448
Cites Hum Hered. 2003;56(4):188-99 15031620
Cites Science. 2004 Jul 23;305(5683):525-8 15273396
Cites Int J Methods Psychiatr Res. 2004;13(2):93-121 15297906
Cites Nat Genet. 2004 Sep;36(9):949-51 15286789
Cites Am J Psychiatry. 1965 Nov;122(5):509-22 5319766
Cites Arch Gen Psychiatry. 1978 Oct;35(10):1181-5 697536
Cites J Nerv Ment Dis. 1987 Nov;175(11):674-80 3681278
Cites Acta Psychiatr Scand. 1987 Oct;76(4):372-80 3425363
Cites Acta Psychiatr Scand. 1989 Mar;79(3):248-56 2711851
Cites JAMA. 1989 Aug 18;262(7):914-9 2754791
Cites JAMA. 1990 Nov 21;264(19):2524-8 2146410
Cites J Nerv Ment Dis. 1993 Aug;181(8):467-74 8360638
Cites Arch Gen Psychiatry. 1993 Nov;50(11):863-70 8215812
Cites J Clin Psychiatry. 1993 Nov;54(11):405-18 8270583
Cites Arch Gen Psychiatry. 1994 Jan;51(1):8-19 8279933
Cites J Affect Disord. 1993 Oct-Nov;29(2-3):77-84 8300980
Cites Br J Psychiatry. 1994 Mar;164(3):297-304 8199782
Cites J Affect Disord. 1994 Sep;32(1):21-6 7798463
Cites Arch Gen Psychiatry. 1996 Feb;53(2):129-36 8629888
Cites Psychol Med. 1996 May;26(3):477-86 8733206
Cites Am J Psychiatry. 1996 Nov;153(11):1411-7 8890673
Cites J Affect Disord. 1996 Oct 14;40(3):159-68 8897115
Cites Science. 1996 Nov 1;274(5288):740-3 8966556
Cites Stat Med. 1997 Nov 30;16(22):2511-28 9403953
Cites Biometrics. 1997 Dec;53(4):1253-61 9423247
Cites Soc Psychiatry Psychiatr Epidemiol. 1998 Dec;33(12):581-6 9857790
Cites J Cell Biol. 1999 Oct 4;147(1):151-62 10508862
Cites Bioinformatics. 2005 Jan 15;21(2):263-5 15297300
Cites Science. 2005 Feb 18;307(5712):1072-9 15718463
Cites Mol Psychiatry. 2005 Mar;10(3):230-1 15738930
Cites Am J Hum Genet. 2005 May;76(5):887-93 15789306
Cites Soc Sci Med. 2005 Jun;60(11):2549-59 15814180
Cites Genet Epidemiol. 2005 May;28(4):352-67 15761913
Cites Am J Hum Genet. 2005 Jun;76(6):967-86 15834813
Cites Nature. 2005 Oct 27;437(7063):1299-320 16255080
Cites Nat Genet. 2005 Nov;37(11):1217-23 16244653
Cites Genet Epidemiol. 2005 Dec;29(4):299-312 16240443
Cites Nucleic Acids Res. 2006 Jan 1;34(Database issue):D173-80 16381840
Cites Nucleic Acids Res. 2006 Jan 1;34(Database issue):D590-8 16381938
Cites Bioinformatics. 2006 Mar 1;22(5):626-7 16418238
Cites Curr Opin Genet Dev. 2006 Jun;16(3):233-9 16650979
Cites Biostatistics. 2006 Jul;7(3):486-502 16500923
Cites Nat Genet. 2006 Aug;38(8):904-9 16862161
Cites Nat Rev Genet. 2006 Oct;7(10):781-91 16983374
GRANTS
GRANTID AGENCY COUNTRY
G0600204 Medical Research Council United Kingdom
MH081802 NIMH NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
R01 MH059160 NIMH NIH HHS United States
R01 MH059160-04 NIMH NIH HHS United States
R01 MH074027 NIMH NIH HHS United States
R01 MH077139 NIMH NIH HHS United States
R01 MH081802 NIMH NIH HHS United States
R01 MH081802-01 NIMH NIH HHS United States
R01 MH084022 NIMH NIH HHS United States
R01 MH084022-01A1 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Adult
Case-Control Studies
Cohort Studies
Cytoskeletal Proteins genetics
Depressive Disorder, Major genetics
Female genetics
Genetic Linkage genetics
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Middle Aged methods
Neuropeptides genetics
Polymorphism, Single Nucleotide genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Cytoskeletal Proteins
0 Neuropeptides
0 PCLO protein, human
OTHER ID's
OTHERID SOURCE
NIHMS75279 NLM
PMC2717726 NLM