Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures

Naomi R. Wray, Michael R. James, Scott D. Gordon, Troy Dumenil, Leanne Ryan, William L. Coventry, Dixie J. Statham, Michele L. Pergadia, Pamela A.F. Madden, Andrew C. Heath, Grant W. Montgomery, Nicholas G. Martin

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

Background: 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. Methods: 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). Results: 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). Conclusions: 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.

Original languageEnglish
Pages (from-to)468-476
Number of pages9
JournalBiological Psychiatry
Volume66
Issue number5
DOIs
StatePublished - Sep 1 2009

Keywords

  • 5HTTLPR
  • SLC6A4
  • SNP
  • anxiety
  • depression
  • extraversion
  • genetic association
  • harm avoidance
  • neuroticism
  • serotonin transporter

Fingerprint

Dive into the research topics of 'Accurate, Large-Scale Genotyping of 5HTTLPR and Flanking Single Nucleotide Polymorphisms in an Association Study of Depression, Anxiety, and Personality Measures'. Together they form a unique fingerprint.

Cite this