title: Case-control association study of TGOLN2 in attempted suicide.
abstract: Family, twin, and adoption studies provide convincing evidence for a genetic contribution to suicidal behavior. The heritability for suicidal behavior depends in part on the transmission of psychiatric disorders, such as mood disorders and substance use disorders, but is also partly independent of them. Three linkage studies using the attempted suicide phenotype in pedigrees with bipolar disorder, major depression, or alcoholism have provided consistent evidence that 2p11-12 harbors a susceptibility gene for attempted suicide. A microarray expression study using postmortem brain samples has implicated a gene from the 2p11-12 candidate region, the trans-Golgi network protein 2 (TGOLN2) gene, as being consistently up-regulated in suicide cases as compared to controls. Here, we present a TGOLN2 case-control association study using nine single nucleotide polymorphisms (SNPs). These nine SNPs, which include seven tag SNPs and two coding SNPs, have been genotyped in 517 mood disorder subjects with a history of attempted suicide and 515 normal controls. Allelic and genotypic analyses of the case-control sample did not provide evidence for association with the attempted suicide phenotype. Eight of the nine SNPs provided supportive evidence for association (P-values ranging from 0.008 to 0.03) when we compared the attempted suicide cases with a history of alcoholism to the attempted suicide cases without a history of alcoholism. However, this association finding was not replicated in an independent sample. Taken together, these analyses do not provide support for the hypothesis that common genetic variation in TGOLN2 contributes significantly to the risk for attempted suicide in subjects with major mood disorders.
authors.affiliation: Department of Psychiatry, Johns Hopkins School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Pamela B
authors.initials: PB
authors.lastname: Mahon
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Stütz
authors.forename: Fayaz
authors.initials: F
authors.lastname: Seifuddin
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Huo
authors.forename: Fernando S
authors.initials: FS
authors.lastname: Goes
authors.forename: Dubravka
authors.initials: D
authors.lastname: Jancic
authors.forename: Jennifer T
authors.initials: JT
authors.lastname: Judy
authors.forename: J Raymond
authors.initials: JR
authors.lastname: Depaulo
authors.forename: Elliot S
authors.initials: ES
authors.lastname: Gershon
authors.forename: Francis J
authors.initials: FJ
authors.lastname: McMahon
authors.forename: Peter P
authors.initials: PP
authors.lastname: Zandi
authors.forename: James B
authors.initials: JB
authors.lastname: Potash
authors.forename: Virginia L
authors.initials: VL
authors.lastname: Willour
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000235:genetics; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013406:Suicide, Attempted
chemical_list: D008562:Membrane Glycoproteins; C072237:TGOLN2 protein, human
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2003 May 15;119B(1):118-30
references.pmid: 12707949
references.citation: Neuropsychobiology. 1981;7(5):248-53
references.pmid: 7312144
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):757-61
references.pmid: 17443717
references.citation: Nature. 1998 Mar 26;392(6674):394-7
references.pmid: 9537323
references.citation: Curr Pharm Des. 2005;11(12):1529-47
references.pmid: 15892660
references.citation: Arch Gen Psychiatry. 1994 Nov;51(11):849-59; discussion 863-4
references.pmid: 7944874
references.citation: Biol Psychiatry. 2009 Apr 1;65(7):556-63
references.pmid: 19201395
references.citation: Arch Gen Psychiatry. 2006 Jan;63(1):35-48
references.pmid: 16389195
references.citation: Arch Gen Psychiatry. 1976 Oct;33(10):1193-7
references.pmid: 971028
references.citation: Arch Gen Psychiatry. 1986 Oct;43(10):962-5
references.pmid: 3753161
references.citation: Nat Genet. 2005 Nov;37(11):1217-23
references.pmid: 16244653
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Alcohol Clin Exp Res. 2004 May;28(5 Suppl):70S-76S
references.pmid: 15166638
references.citation: Am J Hum Genet. 2007 Sep;81(3):559-75
references.pmid: 17701901
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2004 Aug 15;129B(1):47-54
references.pmid: 15274040
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Am J Psychiatry. 2003 Aug;160(8):1486-93
references.pmid: 12900312
references.citation: Am J Psychiatry. 2007 Aug;164(8):1229-37
references.pmid: 17671286
references.citation: Am J Med Genet. 1997 May 31;74(3):227-37
references.pmid: 9184304
references.citation: Biol Psychiatry. 2007 Mar 1;61(5):725-7
references.pmid: 17046723
references.citation: Compr Psychiatry. 2005 Mar-Apr;46(2):81-9
references.pmid: 15723023
references.citation: Arch Gen Psychiatry. 1990 Apr;47(4):383-92
references.pmid: 2181963
references.citation: Mol Psychiatry. 2009 Aug;14(8):755-63
references.pmid: 19488044
references.citation: Science. 2002 Jun 21;296(5576):2225-9
references.pmid: 12029063
references.citation: Psychiatr Clin North Am. 2008 Jun;31(2):179-203
references.pmid: 18439443
references.citation: Am J Psychiatry. 2007 Sep;164(9):1364-70
references.pmid: 17728421
references.citation: J Cell Sci. 1996 Mar;109 ( Pt 3):675-85
references.pmid: 8907712
references.citation: Science. 2003 Jul 18;301(5631):379-83
references.pmid: 12843397
references.citation: Science. 2001 Jul 20;293(5529):506-9
references.pmid: 11441147
references.citation: Annu Rev Genomics Hum Genet. 2009;10:387-406
references.pmid: 19715440
references.citation: Am J Med Genet C Semin Med Genet. 2005 Feb 15;133C(1):13-24
references.pmid: 15648081
references.citation: Am J Hum Genet. 2009 Feb;84(2):210-23
references.pmid: 19200528
references.citation: Br J Psychiatry. 1974 Oct;125(0):355-73
references.pmid: 4425774
references.citation: Nat Genet. 2006 Aug;38(8):904-9
references.pmid: 16862161
references.citation: Am J Psychiatry. 1993 Jun;150(6):935-40
references.pmid: 8494072
references.citation: Acta Psychiatr Scand. 1996 Oct;94(4):234-40
references.pmid: 8911558
references.citation: Mol Psychiatry. 2007 Jul;12(7):630-9
references.pmid: 17505464
references.citation: Am J Psychiatry. 2009 May;166(5):540-56
references.pmid: 19339359
references.citation: Mol Psychiatry. 2006 Mar;11(3):252-60
references.pmid: 16402137
references.citation: Am J Psychiatry. 2008 Apr;165(4):497-506
references.pmid: 18198266