Role of the serotonin transporter promoter polymorphism in anxiety-related traits.
BACKGROUND
The heritability of interindividual variation in anxiety and other aspects of personality establishes that variants of genes influence these traits. A functional polymorphism in the promoter of the human serotonin transporter gene (SLC6A4*C) was identified and found to be linked to an anxiety-related personality trait, Neuroticism. The polymorphism affects gene transcription and, ultimately, gene function. We have attempted to confirm the role of SLC6A4*C in anxiety-related personality traits by sibpair analysis and association studies.


METHODS
Sibpair linkage analysis and association study were performed in 655 Finns. The index cases were 182 alcoholic criminal offenders, through which 258 relatives were ascertained to obtain 366 sibpairs. In addition, 215 unrelated population controls were collected. Each individual was psychiatrically interviewed, blind-rated for DSM-III-R diagnoses, and assessed with the Tridimensional Personality Questionnaire.


RESULTS
The sibpair analysis revealed a positive linkage between SLC6A4*C and the 2 anxiety-related subdimensions of Harm Avoidance: HA1 (Anticipatory Worry) and HA2 (Fear of Uncertainty) (P = .003). However, there was no consistent association between SLC6A4*C and any Tridimensional Personality Questionnaire trait.


CONCLUSIONS
In the present study we replicated the relationship of SLC6A4*C to anxiety by sibpair linkage analysis but found no evidence of association, raising the question of whether SLC6A4*C locus is itself affecting anxiety or is linked to another still unknown functional variant.
Laboratory of Neurogenetics, National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, MD 20852, USA.
C M
CM
Mazzanti
J
J
Lappalainen
J C
JC
Long
D
D
Bengel
H
H
Naukkarinen
M
M
Eggert
M
M
Virkkunen
M
M
Linnoila
D
D
Goldman
D000437:Alcoholism / Q000235:genetics; D001007:Anxiety / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D003415:Crime; D008040:Genetic Linkage; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010551:Personality / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D012701:Serotonin / Q000235:genetics* / Q000502:physiology; D050486:Serotonin Plasma Membrane Transport Proteins; D014158:Transcription, Genetic / Q000502:physiology
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin