TABLE 1

Loci associated with fasting proinsulin levels at genome-wide levels of statistical significance

SNPNearest geneCHRPositionAllele (effect/other)Freq.Discovery P value (n = 10,538–10,701)Replication β (SE) (n = 5,894–15,898)Replication β (SE), BMI adjusted (n = 5,893–15,890)Replication β (SE), BMI + FG adjusted (n = 5,744–15,741)Combined P value (n = 19,168–26,599)Heterogeneity I2 in % (Q-test P value)
rs11603334ARAP11172110633A/G0.153.3 × 10−380.0928 (0.0053)0.0943 (0.0056)0.0938 (0.0052)3.2 × 10−10277.2 (1.9 × 10−7)
rs10501320MADD1147250375G/C0.722.1 × 10−450.0805 (0.0064)0.0748 (0.0069)0.0775 (0.0064)1.1 × 10−8868.1 (8.7 × 10−4)
rs6235PCSK1595754654G/C0.287.7 × 10−140.0394 (0.005)0.0407 (0.0052)0.0438 (0.0049)9.8 × 10−2730.2 (0.14)
rs7903146TCF7L210114748339T/C0.303.5 × 10−180.0321 (0.007)0.0330 (0.0076)0.0303 (0.0063)2.3 × 10−2066.2 (1.6 × 10−3)
rs4502156VPS13C/C2CD4A/B1560170447T/C0.583.8 × 10−110.0294 (0.0044)0.0278 (0.0046)0.0260 (0.0043)3.5 × 10−2045.1 (0.03)
rs11558471SLC30A88118254914A/G0.694.2 × 10−130.0280 (0.0049)0.0280 (0.0053)0.0273 (0.0048)3.1 × 10−1858.5 (0.01)
rs10838687MADD (2nd signal)*1147269468T/G0.808.6 × 10−70.0253 (0.0050)0.0240 (0.0049)0.0246 (0.0049)6.9 × 10−1218.4 (0.26)
rs1549318LARP61568896201T/C0.618.0 × 10−80.0192 (0.0051)0.0209 (0.0056)0.0180 (0.005)2.4 × 10−1052.7 (0.02)
rs4790333SGSM2172209453T/C0.452.2 × 10−80.0154 (0.0043)0.0205 (0.0046)0.0179 (0.0042)3.0 × 10−956.8 (3.5 × 10−3)
rs9727115SNX7**198949841G/A0.645.3 × 10−60.0133 (0.0051)0.0130 (0.005)0.0134 (0.0045)2.4 × 10−70.00 (0.65)
  • β-Coefficients for the effect allele are shown after adjustments for sex, age, geographic covariates (if applicable), and age squared (Framingham only), besides the additional adjustments denoted in the column headings. The combined P values are shown for the joint analysis with the basic adjustments listed above. CHR, chromosome; Freq., frequency.

  • *This second SNP in MADD was selected for further testing based on a suggestive P value (8.6 × 10−7) when analyses for chromosome 11 were conditioned for the top two signals (MADD and ARAP1). The conditional analysis results are shown.

  • **SNX7 only reached genome-wide significance after adjusting for fasting glucose (P = 5.4 × 10−9). Another signal (rs306549 in DDX31) reached genome-wide significance in women (P = 2.0 × 10−8) but not in men (P = 0.17); see text for details.