Table 1

Lead variants associated with HbA1c in East Asians

AnalysisVariant nameChrPositionEA/NEAModelSingle-variant association
nStudies, nEAFEffect (%)SEEffect (mmol/mol)SEP valuePhet
Men onlyrs72554665 (G6PD-Canton)X153760484A/CMen284450.022−0.380.03−4.230.291.25×10−275.13×10−04
Women283660.018−0.220.04−2.470.421.40×10−07
Sex combined5680110.020−0.330.02−3.650.243.00×10−30
Women onlyrs148112010X154 409 817G/AMen284450.026−0.310.02−3.450.246.19×10−274.29×10−04
Women394780.016−0.180.03−1.950.355.39×10−08
Sex combined6791130.020−0.270.02−2.960.201.24×10−28
Sex combinedX153 734 352A/GMen284450.022−0.390.03−4.270.301.35×10−276.70×10−04
Women283660.018−0.230.04−2.520.429.16×10−08
Sex combined5680110.020−0.340.02−3.690.241.71×10−30
Conditioned on G6PD-Canton (rs72554665)
 Men onlyrs72554665 (G6PD-Canton)X153 760 484A/C
 Women onlyrs148112010X154 409 817G/AMen284450.03−0.170.06−1.830.640.730
Women283660.020.120.111.371.180.632
Sex combined5680110.02−0.100.05−1.110.560.923
 Sex combinedX153 734 352A/GMen284450.020.470.725.197.920.789
Women283660.02−1.100.68−12.157.470.994
Sex combined5680110.02−0.360.49−3.985.430.856
  • Samples included in association analyses are type 2 diabetes free: no self-reported diabetes and not on diabetes medication use and (fasting glucose <126 mg/dL (7mmol/L) or random glucose <200 mg/dL (11.1mmol/L) where available) and HbA1c <6.5% (48 mmol/mol).

  • Three different lead variants were identified from association analysis in men only (G6PD-Canton/rs72554665), women only (rs148112010) and sex combined (ChrX:153734352). Associations of rs148112010 and ChrX:153734352 with HbA1c disappeared upon conditioning on G6PD-Canton (rs72554665).

  • Effect allele frequency denotes sample size weighted allele frequency across all studies. P values are obtained from sample size weighted meta-analysis using derived inverse-normalized residuals of HbA1c (%) after adjustment for age, age2 and first three principal components. Effect and SE shown are per allele effect for untransformed HbA1c trait values, assuming that males are homozygous diploid in non-pseudoautosomal region. Phet refers to test of heterogeneity between men and women.

  • As hemizygous males were coded as '2' and males with no variant were coded as '0', the difference in HbA1c between hemizygous males and males with no variant is estimated to be two times the beta effect estimate from regression models (ie, −0.38×2=−0.76)%.

  • Chr, chromosome; EA, effect allele; EAF, effect allele frequency; n, sample size; NEA, non-effect allele.