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      We thank Sand et al. for pointing out two inaccuracies in our article (
      • Talkowski M.E.
      • Mansour H.
      • Chowdari K.V.
      • Wood J.
      • Butler A.
      • Varma P.G.
      • et al.
      Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples.
      ): a typographical error in our previously published Figure 1, and nomenclature problems in previously published Table 1. On the basis of these errors, Sand et al. suggest that our reported associations are invalid. Although we regret these errors, which are corrected herein, they do not alter our interpretation of the data, contrary to Sand et al.’s assertions.
      Figure thumbnail gr1
      Figure 1Dopamine D3 receptor (DRD3) genomic organization and single nucleotide polymorphisms (SNPs) investigated in the United States sample. Known exons are numbered as well as an additional exon (numbered 0) suggested by Anney et al. (
      • Anney R.J.
      • Rees M.I.
      • Bryan E.
      • Spurlock G.
      • Williams N.
      • Norton N.
      • et al.
      Characterization, mutation detection, and association analysis of alternative promoters and 5’ UTRs of the human dopamine D3 receptor gene in schizophrenia.
      ). *Associated SNP in US analyses.
      Table 1SNP-Based Results Across Samples
      US Samples India Trios
      SNP # SNP Location Nuc Strand Allele Code
      Frequency of the allele provided in cases and control subjects.
      Freq. (Case/ Control)
      Trends test p values from genotype distributions.
      Case-Control p
      GC Corrected p TDT (T/NT) TDT p TDT (T/NT) TDT p
      1 rs905568 5′ C + 2 .48/.37 <.0001 .0008 78/72 .62 51/47 .69
      2 rs2399504 5′ C + 1 .82/.81 .923 .933 49/36 .16 28/27 .89
      rs7616367 5′ A + 2 .74/.74 .944 .95 66/43 .02
      3 rs1394016 5′ T
      Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
      2 .37/.33 .145 .194 77/62 .2 64/46 .07
      4 rs1503670 5′ G + 1 .63/.64 .72 .75 83/65 .14 74/64 .39
      5 rs1800828 5′ G 1 .80/.77 .175 .23 62/39 .02 59/45 .17
      6 rs324026 5′ T
      Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
      + 2 .69/.68 .62 .66 78/59 .1 70/56 .21
      7 rs6280 Exon A
      Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
      1 .75/.67 .001 .004 71/54 .13 70/60 .36
      8 rs324029 Intron C
      Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
      2 .73/.72 .855 .87 72/50 .04 60/42 .07
      rs7625282 Intron T 2 .77/.76 .776 .806 71/45 .01
      9 rs324030 Intron C
      Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
      + 2 .72/.73 .813 .83 72/49 .04 59/44 .14
      10 rs2134655 Intron G 2 .73/.67 .022 .075 65/53 .27 48/42 .53
      11 rs10934254 3’ C 1 .44/.39 .073 .12 80/57 .05 71/48 .03
      Nucleotide, strand designations, and/or allele codes (columns 4, 5, and 6) have been corrected so as to make them compatible with HapMap while retaining the integrity of the dataset presented in our earlier manuscript. The single nucleotide polymorphism (SNP) # is given in sequential order according to dopamine D3 receptor (DRD3) transcription (5’ to 3’) from the most upstream (telomeric) to downstream (centromeric) SNP. The SNP # is only given for SNPs assayed in both samples.
      Nuc, nucleotide; T, transmitted allele; NT, not transmitted allele (TDT).
      a Frequency of the allele provided in cases and control subjects.
      b Trends test p values from genotype distributions.
      c Nucleotide provided is designated as “other” allele, not “reference” allele by HapMap (3).
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      References

        • Talkowski M.E.
        • Mansour H.
        • Chowdari K.V.
        • Wood J.
        • Butler A.
        • Varma P.G.
        • et al.
        Novel, replicated associations between dopamine D3 receptor gene polymorphisms and schizophrenia in two independent samples.
        Biol Psychiatry. 2006; 60: 570-577
        • Brookes K.
        • Xu X.
        • Chen W.
        • Zhou K.
        • Neale B.
        • Lowe N.
        • et al.
        The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: Association signals in DRD4, DAT1 and 16 other genes.
        Mol Psychiatry. 2006; 11: 934-953
        • HapMap
        The International HapMap Project.
        Nature. 2003; 426: 789-796
        • Anney R.J.
        • Rees M.I.
        • Bryan E.
        • Spurlock G.
        • Williams N.
        • Norton N.
        • et al.
        Characterization, mutation detection, and association analysis of alternative promoters and 5’ UTRs of the human dopamine D3 receptor gene in schizophrenia.
        Mol Psychiatry. 2002; 7: 493-502
        • Stephens M.
        • Smith N.J.
        • Donnelly P.
        A new statistical method for haplotype reconstruction from population data.
        Am J Hum Genet. 2001; 68 (978–689)
        • Stephens M.
        • Donnelly P.
        A comparison of bayesian methods for haplotype reconstruction from population genotype data.
        Am J Hum Genet. 2003; 73: 1162-1169

      Linked Article

      • A Putative DRD3 Schizophrenia Risk Haplotype Deconstructed
        Biological PsychiatryVol. 63Issue 3
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          Talkowski et al. (1) have claimed an association of schizophrenia with the DRD3 gene in a study using a combined case-control and family-based approach. According to their findings, a five-marker haplotype was overtransmitted to affected offspring in two cohorts of Indian and U.S. origin and was also associated with the disease in a U.S.-based case-control study. Having reviewed these data, we wish to voice concerns over the results and their presentation.
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      • Erratum
        Biological PsychiatryVol. 63Issue 3
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          Several 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.
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