title: Variants of the serotonin transporter gene and NEO-PI-R Neuroticism: No association in the BLSA and SardiNIA samples.
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.
authors.affiliation: National Institute on Aging, NIH, DHHS, Baltimore, Maryland 21224, USA. terraccianoa@mail.nih.gov
authors.forename: Antonio
authors.initials: A
authors.lastname: Terracciano
authors.forename: Lenuta
authors.initials: L
authors.lastname: Balaci
authors.forename: Jason
authors.initials: J
authors.lastname: Thayer
authors.forename: Matthew
authors.initials: M
authors.lastname: Scally
authors.forename: Sarah
authors.initials: S
authors.lastname: Kokinos
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Alan B
authors.initials: AB
authors.lastname: Zonderman
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Nazario
authors.initials: N
authors.lastname: Olla
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zuncheddu
authors.forename: Silvia
authors.initials: S
authors.lastname: Naitza
authors.forename: Fabio
authors.initials: F
authors.lastname: Busonero
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Paul T
authors.initials: PT
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001008:Anxiety Disorders / Q000453:epidemiology / Q000235:genetics; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009497:Neurotic Disorders / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D055815:Young Adult
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins