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.
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.
Authors: Erika J Wolf; Karen S Mitchell; Mark W Logue; Clinton T Baldwin; Annemarie F Reardon; Alison Aiello; Sandro Galea; Karestan C Koenen; Monica Uddin; Derek Wildman; Mark W Miller Journal: J Trauma Stress Date: 2014-08
Authors: Tiffany A Greenwood; Laura C Lazzeroni; Sarah S Murray; Kristin S Cadenhead; Monica E Calkins; Dorcas J Dobie; Michael F Green; Raquel E Gur; Ruben C Gur; Gary Hardiman; John R Kelsoe; Sherry Leonard; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Nicholas J Schork; Larry J Seidman; Larry J Siever; Jeremy M Silverman; William S Stone; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Robert Freedman; David L Braff Journal: Am J Psychiatry Date: 2011-04-15 Impact factor: 18.112
Authors: Hader A Mansour; Michael E Talkowski; Joel Wood; Kodavali V Chowdari; Lora McClain; Konasale Prasad; Debra Montrose; Andrea Fagiolini; Edward S Friedman; Michael H Allen; Charles L Bowden; Joseph Calabrese; Rif S El-Mallakh; Michael Escamilla; Stephen V Faraone; Mark D Fossey; Laszlo Gyulai; Jennifer M Loftis; Peter Hauser; Terence A Ketter; Lauren B Marangell; David J Miklowitz; Andrew A Nierenberg; Jayendra Patel; Gary S Sachs; Pamela Sklar; Jordan W Smoller; Nan Laird; Matcheri Keshavan; Michael E Thase; David Axelson; Boris Birmaher; David Lewis; Tim Monk; Ellen Frank; David J Kupfer; Bernie Devlin; Vishwajit L Nimgaonkar Journal: Bipolar Disord Date: 2009-11 Impact factor: 6.744
Authors: Daniel Mamah; Michael P Harms; Lei Wang; Deanna Barch; Paul Thompson; Jaeyun Kim; Michael I Miller; John G Csernansky Journal: Biol Psychiatry Date: 2008-03-04 Impact factor: 13.382