rs183294

This PhD thesis presents four genetic and epigenetic studies investigating risk factors for suicidal behavior in schizophrenia. Study 1 (n=241 schizophrenia patients) found that only rs2661319 in RGS4 was significantly associated with suicide attempt (p=0.002) among 384 SNPs tested, with RGS4 showing lower potential methylation in attempters (55% vs 65%, p=0.005). Studies 2-4 examined HTR2A and HTR1B methylation and expression in smaller samples (n=47-80) but found no strong evidence that genetic or epigenetic factors significantly predict suicidal behavior. Overall conclusion: no robust genetic or epigenetic predictors of suicide were identified in this schizophrenia population.

This study reports a narrow and highly significant linkage signal for bipolar disorder type I (BP-I) on chromosome 5q33 in Costa Rican and Colombian pedigrees. Fine-mapping with 1,134 SNPs yielded a combined LOD score of 4.9 at rs10035961 (156.9 Mb), with two additional SNPs (rs7721142 and rs1422795) also showing LOD>4 in a 94 kb region. Population-based association analysis identified signals at rs12523547 (P=0.00004) and rs267015 (P=0.00016), though these did not clearly overlap with the linkage peak, suggesting possible allelic or locus heterogeneity.

This two-stage candidate gene association study examined 26 SNPs across four GABA receptor genes (GABRA2, GABRA3, GABRA6, GABRG2) in 589 cases and 539 controls selected for extremes of genetic risk for anxiety disorders, depression, and neuroticism. Two GABRA3 markers showed suggestive association in stage 1 (p ≤ 0.1) but failed to replicate in the larger stage 2 sample (allelic p = 0.63 and 0.32). The study concluded that common variation in these four GABA receptor genes does not play a major role in anxiety spectrum disorder liability.