Homeobox genes in obsessive-compulsive disorder

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.