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.
Key Words
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Article info
Publication history
Published online: June 22, 2009
Accepted:
April 15,
2009
Received in revised form:
March 23,
2009
Received:
December 11,
2008
Identification
Copyright
© 2009 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
