rs686

A systematic review of 98 studies investigating biological predictors of clozapine response in treatment-resistant schizophrenia. Of 70 genetic studies examining 379 variants, only three genetic variants have independently replicated findings: DRD3 Ser9Gly (rs6280), HTR2A His452Tyr, and GNB3 C825T (rs5442/rs5443). Non-genetic predictors include higher prefrontal cortical structural integrity and activity, and lower HVA:5-HIAA ratio in cerebrospinal fluid.

This case-control association study of 650 German migraine with aura (MA) patients and 650 controls tested 53 variants across 10 dopaminergic system genes. Three SNPs in the dopamine-beta hydroxylase (DBH), dopamine transporter (SLC6A3), and dopamine D2 receptor (DRD2) genes showed significant associations with MA. After gene-wide correction, rs2097629 in DBH (OR=0.77, p=0.0012) and rs40184 in SLC6A3 (OR=0.81, p=0.0082) remained significant, with supporting evidence from 2,937 British controls. These findings provide genetic evidence for dopaminergic system involvement in MA pathogenesis.

Family-based association study of 2,037 participants examining five DRD1 polymorphisms in relation to nicotine dependence. rs686 and rs4532 showed significant associations with nicotine dependence measures (FTND, HSI, SQ) in African American and pooled samples (P=0.0048-0.035), with rs686 remaining significant after multiple testing correction. Functional studies demonstrated rs686 in the 3' UTR causes differential DRD1 expression (~27% reduction with G allele, P<0.05).