Summary: Genome-Wide Association Scan of Trait Depression
Antonio Terracciano, Toshiko Tanaka, Angelina R. Sutin, Serena Sanna, Barbara Deiana, Sandra Lai,
Manuela Uda, David Schlessinger, Gonšalo R. Abecasis, Luigi Ferrucci, and Paul T. Costa Jr.
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
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.
Key Words: Depression, GRM8, GWA, mGlu8, neuroticism, RORA
epressed mood is the predominant feature in the diagnosis
of mood disorders (e.g., major depressive disorder, dysthy-