G-protein β3 subunit genetic variation moderates five-year depressive symptom trajectories of primary care attendees

Background: Genetic variation in the G-protein β3 subunit (GNB3) has previously been associated with gene splicing that has been further linked to increased signal transduction and major depressive disorder. However, the effect of GNB3 genetic variation on depressive symptom trajectories is currently unknown. The aim of the present study is to examine whether genetic variation in GNB3 moderates depressive symptom trajectories among 301 primary care attendees enrolled in the Diagnosis, Management and Outcomes of Depression in Primary Care (diamond) prospective cohort study.

Methods: Depressive symptoms were assessed using three measures: (1) DSM-IV criteria, (2) Primary Care Evaluation of Mental Disorders Patient Health Questionnaire-9 (PHQ-9), and (3) Center for Epidemiologic Studies Depression Scale (CESD). DSM-IV criteria were measured at baseline, 24, 36, 48, and 60 months post-baseline, whereas, PHQ-9 and CESD measurements were taken at baseline, 12, 24, 36, 48, and 60 months post-baseline. Two haplotype-tagging single nucleotide polymorphisms [rs5443 (C825T) and rs5440] spanning the GNB3 gene including ~1Kb upstream and downstream of the gene boundaries were genotyped.

Results: Five-year PHQ-9 and CESD depressive symptom trajectories were moderated by rs5440. Carriers of the rs5440 GG genotype had more favourable depressive symptom trajectories compared to AG or AA genotype carriers. The rs5443 polymorphism did not moderate depressive symptom trajectories, regardless of the measure used.

Limitations: Generalizability to depressed populations outside of the primary care setting may be limited.

Conclusions: These results provide novel evidence suggesting genetic variation in the 5-prime region of GNB3 moderates depressive symptom trajectories among primary care attendees.