title: Homeobox genes in obsessive-compulsive disorder.
abstract: BACKGROUND
  Despite evidence that obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition, progress aimed at identifying genetic determinants of the disorder has been slow. The OCD Collaborative Genetics Study (OCGS) has identified several OCD susceptibility loci through linkage analysis.
  
  
  METHODS
  In this study we investigate two regions on chromosomes 15q and 1q by first refining the linkage region using additional short tandem repeat polymorphic (STRP) markers. We then performed association analysis on single nucleotide polymorphisms (SNP) genotyped (markers placed every 2-4 kb) in the linkage regions in the OCGS sample of 376 rigorously phenotyped affected families.
  
  
  RESULTS
  Three SNPs are most strongly associated with OCD: rs11854486 (P = 0.00005 [0.046 after adjustment for multiple tests]; genetic relative risk (GRR) = 11.1 homozygous and 1.6 heterozygous) and rs4625687 [P = 0.00007 (after adjustment = 0.06); GRR = 2.4] on 15q; and rs4387163 (P = 0.0002 (after adjustment = 0.08); GRR = 1.97) on 1q. The first SNP is adjacent to NANOGP8, the second SNP is in MEIS2, and the third is 150 kb between PBX1 and LMX1A.
  
  
  CONCLUSIONS
  All the genes implicated by association signals are homeobox genes and are intimately involved in neurodevelopment. PBX1 and MEIS2 exert their effects by the formation of a heterodimeric complex, which is involved in development of the striatum, a brain region involved in the pathophysiology of OCD. NANOGP8 is a retrogene of NANOG, a homeobox transcription factor known to be involved in regulation of neuronal development. These findings need replication; but support the hypothesis that genes involved in striatal development are implicated in the pathogenesis of OCD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA. gnestadt@jhmi.edu
authors.forename: G
authors.initials: G
authors.lastname: Nestadt
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: M A
authors.initials: MA
authors.lastname: Grados
authors.forename: M A
authors.initials: MA
authors.lastname: Riddle
authors.forename: B D
authors.initials: BD
authors.lastname: Greenberg
authors.forename: J A
authors.initials: JA
authors.lastname: Knowles
authors.forename: A J
authors.initials: AJ
authors.lastname: Fyer
authors.forename: J T
authors.initials: JT
authors.lastname: McCracken
authors.forename: S L
authors.initials: SL
authors.lastname: Rauch
authors.forename: D L
authors.initials: DL
authors.lastname: Murphy
authors.forename: S A
authors.initials: SA
authors.lastname: Rasmussen
authors.forename: B
authors.initials: B
authors.lastname: Cullen
authors.forename: J
authors.initials: J
authors.lastname: Piacentini
authors.forename: D
authors.initials: D
authors.lastname: Geller
authors.forename: D
authors.initials: D
authors.lastname: Pauls
authors.forename: O J
authors.initials: OJ
authors.lastname: Bienvenu
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: K Y
authors.initials: KY
authors.lastname: Liang
authors.forename: F S
authors.initials: FS
authors.lastname: Goes
authors.forename: B
authors.initials: B
authors.lastname: Maher
authors.forename: A E
authors.initials: AE
authors.lastname: Pulver
authors.forename: Y Y
authors.initials: YY
authors.lastname: Shugart
authors.forename: D
authors.initials: D
authors.lastname: Valle
authors.forename: J F
authors.initials: JF
authors.lastname: Samuels
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
mesh_terms: D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D005801:Genes, Homeobox / Q000235:genetics*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D005819:Genetic Markers
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