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BackgroundThe length polymorphism repeat in the promoter region of the serotonin transporter gene (5HTTLPR) is one of the most studied polymorphisms for association with a range of psychiatric and personality phenotypes. However, the original 5HTTLPR assay is prone to bias toward short allele calling.MethodsWe designed new assays for the 5HTTLPR suitable for large-scale genotyping projects and we genotyped 13 single nucleotide polymorphisms (SNPs) in a 38-kilobase region around the 5HTTLPR, including SNP rs25531, a polymorphism of the 5HTTLPR long allele. Association analysis was conducted for major depression and/or anxiety disorder in unrelated cases (n = 1161) and control subjects (n = 1051) identified through psychiatric interviews administered to a large population sample of Australian twin families. Participants had been scored for personality traits several years earlier (n > or = 2643 unrelated individuals).ResultsWe identified a two-SNP haplotype proxy for 5HTTLPR; the CA haplotype of SNPs rs4251417 and rs2020934 is coupled with the short allele of 5HTTLPR (r(2) = .72). We found evidence for association (p = .0062, after accounting for multiple testing) for SLC6A4 SNPs rs6354 and rs2020936 (positioned in a different linkage disequilibrium [LD] block about 15.5 kb from 5HTTLPR) with anxiety and/or depression and neuroticism, with the strongest association for recurrent depression with onset in young adulthood (odds ratio = 1.55, 95% confidence interval = 1.16-2.06).ConclusionsThe associated SNPs are in the same LD block as the variable number of tandem repeats serotonin transporter intron 2 marker, for which association has previously been reported.

Original publication




Journal article


Biological psychiatry

Publication Date





468 - 476


Genetic and Molecular Epidemiology Laboratories, Queensland Institute of Medical Research, 300 Herston Road, Brisbane 4006, Australia.


Humans, Case-Control Studies, Personality, Anxiety Disorders, Depressive Disorder, Major, Genotype, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Models, Genetic, Adult, Female, Male, Serotonin Plasma Membrane Transport Proteins, Genome-Wide Association Study