Background
Meta-analyses have suggested an association between schizophrenia (SZ) and a coding
polymorphism (rs6280/Ser9Gly) at the dopamine D3 receptor gene (DRD3), but results have been inconsistent.
Because most studies have evaluated only rs6280, the inconsistencies might reflect
associations with other variants.
Methods
We analyzed polymorphisms spanning 109kb in two independent samples (United States:
13 single nucleotide polymorphisms (SNPs), 331 cases, 151 trios, 274 control subjects;
India: 11 SNPs, 141 trios).
Results
In the U.S. samples, significant associations were detected with eight SNPs, including
rs6280 (p = .001, odds ratio: 1.5). Consistent associations in the case-control and family-based
analyses were detected with a common haplotype spanning intron 1 to the 3′ region
of the gene (rs324029-rs7625282-rs324030-rs2134655-rs10934254; case-control, p = .002; transmission disequilibrium test [TDT], p = .0009; global p-values = .002 and .007, respectively). In the Indian sample, one SNP was associated
(rs10934254, p = .03). Moreover, over-transmission of the same common haplotype as the U.S. sample
was observed in this cohort (TDT, p = .005; global test, p = .009). Ser9Gly (rs6280) was associated with SZ against this haplotype background but not other
haplotypes.
Conclusions
These data suggest previous inconsistencies might have resulted from associations
with other DRD3 variants. A liability locus might be in linkage disequilibrium (LD)
with or carried against, an associated haplotype 3′ to rs6280. Comprehensive SNP evaluation
in larger samples is needed.
Key Words
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Article info
Publication history
Published online: August 10, 2006
Accepted:
April 13,
2006
Received in revised form:
March 9,
2006
Received:
July 25,
2005
Identification
Copyright
© 2006 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
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- ErrataBiological PsychiatryVol. 63Issue 10
- PreviewIn Figure 1 of the article “Novel, Replicated Associations Between Dopamine D3 Receptor Gene Polymorphisms and Schizophrenia in Two Independent Samples” by Talkowski et al. (Biol Psychiatry 2006;60:570–577), the authors note that the inter-single nucleotide polymorphism (SNP) distances were based on estimates at the time of SNP discovery in their lab (circa 1999). Some of these distances differ in the current human genome reference sequence. Accordingly, the authors have revised Figure 1 with the genomic location for each SNP, using the current build of dbSNP (National Center for Biotechnology Information [NCBI] dbSNP build 128, released 10/23/2007).
- Full-Text
- Preview
- ErratumBiological PsychiatryVol. 63Issue 3
- PreviewSeveral typographical and nomenclature errors in Figure 1 and Table 1 have been identified in the September 15, 2006, issue of Biological Psychiatry, Volume 60, Issue 6, in the article “Novel, Replicated Associations Between Dopamine D3 Receptor Gene Polymorphisms and Schizophrenia in Two Independent Samples” by Talkowski et al. (Biol Psychiatry 2006;60:570-577). The authors note that the errors, detailed below, do not alter the statistical analyses or their interpretation of the data.
- Full-Text
- Preview
