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Role of the Serotonin Transporter Promoter Polymorphism in Anxiety-Related Traits
Chiara M. Mazzanti, PhD;
Jaakko Lappalainen, MD, PhD;
Jeffrey C. Long, PhD;
Dietmar Bengel, MD;
Hannu Naukkarinen, MD;
Monica Eggert, MD;
Matti Virkkunen, MD;
Markku Linnoila, MD, PhD;
David Goldman, MD
Arch Gen Psychiatry. 1998;55:936-940.
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.
From the Laboratory of Neurogenetics (Drs Mazzanti and Goldman), Section of Population Genetics and Linkage (Drs Lappalainen and Long), Laboratory of Clinical Studies (Dr Linnoila), National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Md; Department of Psychiatry (Drs Naukkarinen, Eggert, and Virkkunen), University of Helsinki, Helsinki, Finland; and Laboratory of Clinical Science (Dr Bengel), National Institute of Mental Health, National Institutes of Health, Bethesda, Md. Dr Linnoila is deceased.
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