Genome-wide association for major depressive disorder: a possible role for the presynaptic protein piccolo

被引：332

作者：

Sullivan, P. F. ^{[1
]}

de Geus, E. J. C.

Willemsen, G.

James, M. R. ^{[3
]}

Smit, J. H. ^{[2
]}

Zandbelt, T. ^{[2
]}

Arolt, V. ^{[4
]}

Baune, B. T. ^{[5
]}

Blackwood, D. ^{[6
]}

Cichon, S. ^{[7
]}

Coventry, W. L. ^{[8
]}

Domschke, K. ^{[4
]}

Farmer, A. ^{[9
]}

Fava, M. ^{[10
]}

Gordon, S. D. ^{[3
]}

He, Q. ^{[1
]}

Heath, A. C. ^{[11
]}

Heutink, P. ^{[2
]}

Holsboer, F. ^{[12
]}

Hoogendijk, W. J. ^{[2
]}

Hottenga, J. J.

Hu, Y. ^{[1
]}

Kohli, M. ^{[12
]}

Lin, D. ^{[1
]}

Lucae, S. ^{[12
]}

MacIntyre, D. J. ^{[13
]}

Maier, W. ^{[7
]}

McGhee, K. A. ^{[6
]}

McGuffin, P. ^{[9
]}

Montgomery, G. W. ^{[3
]}

Muir, W. J. ^{[6
]}

Nolen, W. A. ^{[14
]}

Noethen, M. M. ^{[7
]}

Perlis, R. H. ^{[10
]}

Pirlo, K. ^{[9
]}

Posthuma, D.

Rietschel, M. ^{[15
]}

Rizzu, P. ^{[2
]}

Schosser, A. ^{[9
]}

Smit, A. B.

Smoller, J. W. ^{[10
]}

Tzeng, J-Y ^{[16
]}

van Dyck, R. ^{[2
]}

Verhage, M.

Zitman, F. G. ^{[17
]}

Martin, N. G. ^{[3
]}

Wray, N. R. ^{[3
]}

Boomsma, D. I.

Penninx, B. W. J. H. ^{[2
]}

机构：

[1] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA

[2] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands

[3] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[4] Univ Munster, Munster, Germany

[5] James Cook Univ, Cairns, Qld, Australia

[6] Univ Edinburgh, Edinburgh, Midlothian, Scotland

[7] Univ Bonn, D-5300 Bonn, Germany

[8] Univ New England, Armidale, NSW, Australia

[9] Inst Psychiat, London, England

[10] Harvard Univ, Sch Med, Cambridge, MA 02138 USA

[11] Washington Univ, St Louis, MO USA

[12] Max Planck Inst Psychiat, D-80804 Munich, Germany

[13] Royal Edinburgh & Associated Hosp, Edinburgh, Midlothian, Scotland

[14] Univ Groningen, Univ Med Ctr Groningen, NL-9713 AV Groningen, Netherlands

[15] Heidelberg Univ, Heidelberg, Germany

[16] N Carolina State Univ, Raleigh, NC 27695 USA

[17] Leiden Univ, Med Ctr, Leiden, Netherlands

来源：

MOLECULAR PSYCHIATRY | 2009年 / 14卷 / 04期

基金：

奥地利科学基金会;

关键词：

major depressive disorder; genome-wide association; Netherlands study of depression and anxiety; Netherlands twin registry; FALSE DISCOVERY RATE; SINGLE-NUCLEOTIDE POLYMORPHISMS; SAMPLE-SIZE REQUIREMENTS; COPY-NUMBER VARIATION; SELECTION BIAS; PSYCHIATRIC-PATIENTS; HAPLOTYPE MAP; TWIN REGISTER; GENE; DATABASE;

D O I：

10.1038/mp.2008.125

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：359 / 375

页数：17

共 109 条

[1]

A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[2]

Guilt beyond a reasonable doubt [J].

Altshuler, David ;

Daly, Mark .

NATURE GENETICS, 2007, 39 (07) :813-815

[3]

[Anonymous], 1993, Composite International Diagnostic Interview (CIDI)

[4]

[Anonymous], 2004, SAS STAT SOFTW VERS

[5]

A tutorial on statistical methods for population association studies [J].

Balding, David J. .

NATURE REVIEWS GENETICS, 2006, 7 (10) :781-791

[6]

Haploview: analysis and visualization of LD and haplotype maps [J].

Barrett, JC ;

Fry, B ;

Maller, J ;

Daly, MJ .

BIOINFORMATICS, 2005, 21 (02) :263-265

[7]

A genome-wide association study implicates diacylglycerol kinase η (DGKH) and several other genes in the etiology of bipolar disorder [J].

Baum, A. E. ;

Akula, N. ;

Cabanero, M. ;

Cardona, I. ;

Corona, W. ;

Klemens, B. ;

Schulze, T. G. ;

Cichon, S. ;

Rietschel, M. ;

Noethen, M. M. ;

Georgi, A. ;

Schumacher, J. ;

Schwarz, M. ;

Abou Jamra, R. ;

Hoefels, S. ;

Propping, P. ;

Satagopan, J. ;

Detera-Wadleigh, S. D. ;

Hardy, J. ;

McMahon, F. J. .

MOLECULAR PSYCHIATRY, 2008, 13 (02) :197-207

[8]

CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].

BENJAMINI, Y ;

HOCHBERG, Y .

JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300

[9]

MORTALITY IN SEVERE DEPRESSION - A PROSPECTIVE-STUDY INCLUDING 103 SUICIDES [J].

BERGLUND, M ;

NILSSON, K .

ACTA PSYCHIATRICA SCANDINAVICA, 1987, 76 (04) :372-380

[10]

LIMITATIONS OF THE APPLICATION OF FOURFOLD TABLE ANALYSIS TO HOSPITAL DATA [J].

BERKSON, J .

BIOMETRICS BULLETIN, 1946, 2 (03) :47-53

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