TABLE 6

Comparison of four GWA studies

FHSMexican AmericanPima C/CPima familyAmish
n1,087281 case/280 control300 case/334 control172 sibships124 case/295 control
TypePopulation, family-basedCase/controlCase/controlFamilyCase/control
EthnicityNon-Hispanic whiteMexican AmericanAmerican IndianAmerican IndianNon-Hispanic white
Male/female527/560
    Case108/173114/18648/9241/83
    Control69/211160/17457/64153/142
Mean age (years)51.5 ± 9.8
    Case57.7 ± 10.819.2 ± 4.541.0 ± 8.351.3 ± 10.5
    Control55.5 ± 9.827.8 ± 7.964.4 ± 12.9
Mean BMI (kg/m2)27.5 ± 5.2
    Case31.5 ± 6.238.9 ± 8.438.9 ± 9.329.3 ± 5.8
    Control35.4 ± 8.036.9 ± 8.927.4 ± 4.7
Quantitative glycemic traits analyzedFPG, tFPG, A1C, FI, HOMA-IR, Gutt ISI 0_120FASTG, glucose AUC, insulin AUC, HOMA-IR, insulin secretion index
Notes91 cases of incident diabetesControlled for admixtureAge of onset <25 yearsSibships overlap with C/CCases have (+) FH; active lifestyle
SNPs analyzed66,54388,70280,04480,04482,485
SNPs failed39,205 MAF <10%; 4,064 HWE P < 0.001; 10,438 call rate <90%19,032 MAF <5%; 1,562 HWE P < 0.001; 4,818 call rate <85%28,215 MAF <1%; 2,429 HWE P < 0.001; 5,122 call rate <85% and/or error rate >3% in duplicate samples28,215 MAF <1%; 2,429 HWE P < 0.001; 5,122 call rate <85% and/or error rate >3% in duplicate samples26,816 MAF <5%; 2,573 HWE P < 0.001; 1,866 call rate <90%
P value thresholdsStrategy 1: P < 0.01 in all three glucose traits (FPG, tFPG, and A1C) or in all 3 insulin traits (FI, HOMA-IR, and Gutt) or two glucose and two insulin traits or incident type 2 diabetes; Strategy 2: P < 0.001Primary analysis: P < 0.01 for type 2 diabetes; In silico replication: P < 0.05In silico replication:P < 0.007 in combined within-family and case-control analysis (weighted to give priority to within-family test); Additional genotyping: P < 0.001 in combined within-family and case-control analysis as aboveIn silico replication: P < 0.007 in combined within-family and case-control analysis (weighted to give priority to within-family test); Additional genotyping: P < 0.001 in combined within-family and case- control analysis as abovePrimary analysis: P < 0.01 for type 2 diabetes; Internal replication: type 2 diabetes P < 0.01 and one glucose trait (FASTG or GAUC) or one insulin trait (ISI, IAUC, or HOMA-IR) P < 0.01
Replication cohort1,465 unrelated FHS participants (non-overlapping)760 overlapping individuals for SNP verificationNon-overlapping Pima Indians: 1,207 case/1,627 controlNon-overlapping Pima Indians: 1,207 case/1,627 control427 nondiabetic Amish participants (295 control from primary type 2 analysis)
In silico replicationT2D 100K Consortium + DGI 500KT2D 100K Consortium + DGI 500KT2D 100K Consortium + DGI 500KT2D 100K Consortium + DGI 500KT2D 100K Consortium + DGI 500K
  • T2D, type 2 Diabetes.