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Variants of the serotonin transporter gene and NEO-PI-R Neuroticism: No association in the BLSA and SardiNIA samples

National Institute on Aging, NIH, DHHS, Baltimore, Maryland 21224, USA.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.27). 03/2009; 150B(8):1070-7. DOI: 10.1002/ajmg.b.30932
Source: PubMed

ABSTRACT The polymorphism in the serotonin transporter gene promoter region (5-HTTLPR) is by far the most studied variant hypothesized to influence Neuroticism-related personality traits. The results of previous studies have been mixed and appear moderated by the personality questionnaire used. Studies that used the TCI to assess Harm Avoidance or the EPQ to assess Neuroticism have found no association with the 5-HTTLPR. However, studies that used the NEO-PI-R or related instruments (NEO-PI, NEO-FFI) to measure Neuroticism have found some evidence of association. This study examines the association of variants in the serotonin transporter gene in a sample from a genetically isolated population within Sardinia (Italy) that is several times larger than previous samples that used the NEO-PI-R (N = 3,913). The association was also tested in a sample (N = 548) from the Baltimore Longitudinal Study of Aging (BLSA), in which repeated NEO-PI-R assessments were obtained. In the SardiNIA sample, we found no significant association of the 5-HTTLPR genotypes with Neuroticism or its facets (Anxiety, Angry-Hostility, Depression, Self-Consciousness, Impulsiveness, and Vulnerability). In the BLSA sample, we found lower scores on Neuroticism traits for the heterozygous group, which is inconsistent with previous studies. We also examined eight SNPs in the SardiNIA (N = 3,972) and nine SNPs in the BLSA (N = 1,182) that map within or near the serotonin transporter gene (SLC6A4), and found no association. Along with other large studies that used different phenotypic measures and found no association, this study substantially increases the evidence against a link between 5-HTT variants and Neuroticism-related traits.

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    • "DNA and self-reports of personality traits were obtained from individuals living in the Ogliastra province of Sardinia (Costa et al., 2007; Pilia et al., 2006; Terracciano et al., 2009). This is a founder population, in which most individuals are descended from a small group of common ancestors with minimal intermarriage with other groups, which leads to greater genetic homogeneity in such groups. "
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    • "This effect differs from those reported in previous smaller studies (Pezawas et al, 2008; Rybakowski et al, 2007; Wichers et al, 2008). Nevertheless, higher scores on neuroticism seem consistent with a synergistic effect of the BDNF Met variant, which reduces BDNF secretion and leads to anxiety-related behaviors in mice (Chen et al, 2006; Egan et al, 2003; Matsuo et al, 2009), and with the 5-HTTLPR LL genotype, which is associated with a higher rate of serotonin re-uptake from the synaptic cleft and supposedly to serotonin depletion (Arbelle et al, 2003; Lesch et al, 1996; Terracciano et al, 2009a). Given our promising findings and the intuitive appeal of an interaction between variants that reduce the circulating level of BDNF and serotonin, larger studies should attempt to confirm this epistatic effect on this major risk factor for depression. "
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