Genome-wide association scan of trait depression.

BACKGROUND Independent of temporal circumstances, some individuals have greater susceptibility to depressive affects, such as feelings of guilt, sadness, hopelessness, and loneliness. Identifying the genetic variants that contribute to these individual differences can point to biological pathways etiologically involved in psychiatric disorders. METHODS Genome-wide association scans for the depression scale of the Revised NEO Personality Inventory in community-based samples from a genetically homogeneous area of Sardinia, Italy (n = 3972) and from the Baltimore Longitudinal Study of Aging in the United States (n = 839). RESULTS Meta-analytic results for genotyped or imputed single nucleotide polymorphisms indicate that the strongest association signals for trait depression were found in RORA (rs12912233; p = 6 × 10⁻⁷), a gene involved in circadian rhythm. A plausible biological association was also found with single nucleotide polymorphisms within GRM8 (rs17864092; p = 5 × 10⁻⁶), a metabotropic receptor for glutamate, a major excitatory neurotransmitter in the central nervous system. CONCLUSIONS These findings suggest shared genetic basis underlying the continuum from personality traits to psychopathology.