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Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

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Homeobox genes in obsessive-compulsive disorder.

G Nestadt¹, Y Wang, M A Grados

¹Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21287, USA. gnestadt@jhmi.edu

American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics

|November 19, 2011

Summary

Genetic analysis identified three single nucleotide polymorphisms (SNPs) associated with obsessive-compulsive disorder (OCD) on chromosomes 15q and 1q. These findings implicate homeobox genes in striatal development and OCD pathogenesis.

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Exploring the Neural Correlates of Cognitive Reappraisal in Obsessive-Compulsive Disorder Using Task-based Functional Magnetic Resonance Imaging

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Area of Science:

Neurogenetics
Psychiatric Genetics

Background:

Obsessive-compulsive disorder (OCD) is a familial neuropsychiatric condition with identified susceptibility loci.
Genetic determinant identification for OCD has been challenging.

Purpose of the Study:

Investigate specific chromosomal regions (15q and 1q) for genetic associations with OCD.
Refine linkage regions and perform association analysis using single nucleotide polymorphisms (SNPs).

Main Methods:

Utilized the OCD Collaborative Genetics Study (OCGS) sample of 376 families.
Refined linkage regions using short tandem repeat polymorphic (STRP) markers.
Performed association analysis on genotyped SNPs within identified linkage regions.

Main Results:

Identified three SNPs significantly associated with OCD: rs11854486 and rs4625687 on 15q, and rs4387163 on 1q.
rs11854486 is near NANOGP8, rs4625687 is in MEIS2, and rs4387163 is between PBX1 and LMX1A.
Associated genes (NANOGP8, MEIS2, PBX1, LMX1A) are homeobox genes involved in neurodevelopment.

Conclusions:

Homeobox genes implicated in striatal development are potentially involved in OCD pathogenesis.
PBX1 and MEIS2 form a complex crucial for striatal development, a region implicated in OCD.
NANOGP8, a NANOG retrogene, is involved in neuronal development regulation.
Findings require replication but support the role of neurodevelopmental genes in OCD.