Journal article
Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures
Biological Psychiatry, Vol.66(5), pp.468-476
2009
Abstract
The 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. We 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 ≥2643 unrelated individuals). We identified a two-SNP haplotype proxy for 5HTTLPR; the CA haplotype of SNPs rs4251417 and rs2020934 is coupled with the short allele of 5HTTLPR (r2 = .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). The 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.
Details
- Title
- Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures
- Authors
- N R Wray (Author) - Queensland Institute of Medical ResearchM R James (Author) - Queensland Institute of Medical ResearchScott D Gordon (Author) - Queensland Institute of Medical ResearchT Dumenil (Author) - Queensland Institute of Medical ResearchLeanne Ryan (Author) - Queensland Institute of Medical ResearchW L Coventry (Author) - Queensland Institute of Medical ResearchDixie J Statham (Author) - University of the Sunshine Coast - Faculty of Arts and Social SciencesM L Pergadia (Author) - Washington University, United StatesP A F Madden (Author) - Washington University, United StatesA C Heath (Author) - Washington University, United StatesG W Montgomery (Author) - Queensland Institute of Medical ResearchN G Martin (Author) - Queensland Institute of Medical Research
- Publication details
- Biological Psychiatry, Vol.66(5), pp.468-476
- Publisher
- Elsevier Inc.
- Date published
- 2009
- DOI
- 10.1016/j.biopsych.2009.04.030
- ISSN
- 0006-3223
- Copyright note
- Copyright © 2009. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
- Organisation Unit
- School of Social Sciences - Legacy; University of the Sunshine Coast, Queensland
- Language
- English
- Record Identifier
- 99449664902621
- Output Type
- Journal article
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