TABLE 7

Replication evidence across four GWA studies

StudySNPChr.Position (hg17)GeneGene nameOMIMInitial findingQTInternal replicationExternal replication 100K T2D ConsortiumExternal replication 500K DGI
FHSrs9526351p31.266403906PDE4BcAMP-specific phosphodiesterase600127G-allele protective for type 2 diabetes (HR 0.56 [0.40–0.79], Cox P = 0.0007)Same protective allele associated with higher Gutt ISI and lower FPG, mFPG, A1C, and HOMA-IR (GEE P ∼ 0.003)FPG and HOMA-IR (P < 0.05)Nors6664618 in moderate LD (r2 = 0.6); consistent trends in FPG (P = 0.04) and HOMA-IR (P = 0.057)
FHSrs28633893q26.1167631594200 kb from nearest geneN/AMinor T-allele at SNP rs2863389 protective against diabetes (HR 0.41 [0.25–0.69], Cox P = 0.0006)Same protective allele associated with lower FPG and mFPG in the FHS sample (GEE P = 0.005 and 0.0005, respectively)NoT-allele protects from type 2 diabetes in Mexican Americans (OR 0.43, nominal P = 0.03) and in the Amish (OR 0.71, nominal P = 0.04) with similar trends in the Pimasrs9829442 in perfect LD (r2 = 1.0); minor T-allele shows opposite nominal trend in increasing risk of type 2 diabetes (OR 1.15, P = 0.059)
FHSrs793508211q12.259911576MS4A7Membrane-spanning 4-domains subfamily A member 7606502T-allele associated with lower FPG in FHS (FBAT P = 0.0006)SameNoT-allele was nominally protective from diabetes in the Mexican Americans (OR 0.53, P = 0.049) and in the Pimas (OR 0.58, P = 0.009)rs950803 in perfect LD (r2 = 1.0); minor T-allele shows consistent nominal trend in protection from type 2 diabetes (OR 0.89, P = 0.097)
Amishrs22374577p12.250693638GRB10Growth factor receptor bound protein 10601523G-allele protective for type 2 diabetes (OR 0.61, P = 0.00001)Same protective allele associated with lower GAUC (P = 0.001)NoNoNot with rs2237457; six additional GRB10 SNPs in LD (r2 0.16–0.78) are associated with type 2 diabetes (P < 0.05)
Amishrs38459713p14.259975712FHITFragile histidine triad gene601153T-allele increased type 2 diabetes risk (OR 1.42, P = 0.004)Same risk allele associated with increased GAUC (P = 0.0004)NoMexican-American type 2 diabetes OR 1.46 (P = 0.004)No
Pimars1050093811p14.322601179FANCFFanconia anemia, complementation group F603467A-allele increased type 2 diabetes risk (OR 2.14, P = 0.0004)A-allele OR=1.65 (p=0.0010)No(A-allele absent in CEU)
Pimars68698911q23.1113544435ZTBT16Zinc finger and BTB domain containing-16176797A-allele increased type 2 diabetes risk (OR 3.26, P = 0.0004)A-allele OR 1.27 (P = 0.0333)NoNo
MArs97975211p154326380UBQLNLUbiquilin3605473T-allele protective for type 2 diabetes (OR 0.562, P = 0.00012)N/AN/AAmish type 2 diabetes OR 0.764 (P = 0.030) and FHS HRR 0.709 (P = 0.040)No
MArs27730801q25176963373RALGPS2Ral GEF with PH domain and SH3 binding motif 2611154G-allele protective for type 2 diabetes (OR 0.628, P = 0.0008)N/AN/AAmish type 2 diabetes OR 0.793 (P = 0.033)No
MArs150995710q21.164280724EGR2Early growth response 2129010G-allele protective for type 2 diabetes (OR 0.652, P = 0.00084)N/AN/APima type 2 diabetes OR 0.721 (P=0.032)Same SNP OR 0.831 (P = 0.0082)
  • Chr., chromosome.