TABLE 3

SNPs associated with type 2 diabetes (P < 0.01) and at least one OGTT-derived trait (P < 0.01) in nondiabetic Amish subjects

SNPChromo-somePosition*Gene†StrandAlleles 1/2Frequency allele 2Type 2 diabetes
OGTT trait analysis
POR§TraitMean 11Mean 12Mean 22P
rs667222155090696DHCR24A/G0.750.0050.71GAUC212.21199.85192.580.008
rs6588186166319597PDE4BA/G0.780.0081.45GAUC192.09185.94201.070.002
rs570021171217978PTGER3+A/T0.270.0070.70IAUC550.64613.59690.130.007
rs6424414171228058PTGER3+C/T0.270.0070.70IAUC548.85614.86683.350.007
rs211706175802445SLC44A5A/G0.080.0020.52Fasting glucose2.832.742.680.006
rs10493580176277500LOC729766+C/G0.150.0030.60GAUC199.25186.85189.200.005
rs1030414181241030C/T0.070.0050.51GAUC197.22182.88154.780.003
rs22579631105672501C/T0.610.0090.74GAUC208.52195.36190.490.009
rs15161501105758114+A/G0.390.0101.36GAUC190.76195.70208.750.009
rs25762161215202099ESRRG+A/G0.160.0060.64GAUC200.81187.83190.210.002
rs28187811215203396ESRRG+C/T0.840.0031.61GAUC168.17189.21201.242.2 × 10−4
rs25762121215204637ESRRGA/G0.840.0051.58GAUC178.70188.25200.710.001
rs13437471240794106+A/C0.230.0021.43HOMA-IR2.222.532.720.002
IAUC555.29646.59694.290.002
rs10495824234604049C/T0.760.0081.41IAUC677.25635.10545.830.002
rs10490049240426854SLC8A1A/C0.170.0021.54Fasting glucose2.792.882.890.001
GAUC192.09204.49216.330.001
rs897097255539162+A/G0.610.0011.46HOMA-IR2.092.372.490.010
rs25403172102716239MFSD9C/T0.780.0070.72GAUC216.62199.07189.803.4 × 10−4
rs43243362105593460A/T0.780.0051.44Fasting glucose2.782.762.850.002
rs23212012134136406C/T0.370.0061.35IAUC539.03627.77628.080.006
rs10510530322459609+A/T0.860.0030.65Fasting glucose2.902.862.790.007
rs3845971359975712FHIT+C/T0.720.0041.42GAUC185.46188.48203.711.0 × 10−4
rs1373340366984977A/C0.860.0070.67HOMA-IR1.892.142.430.006
IAUC529.61519.62610.680.009
rs25870153147740690PLSCR1C/T0.760.0071.40IAUC751.72609.81547.070.001
rs25870143147741153PLSCR1+A/G0.240.0090.72IAUC548.12610.88743.820.001
rs25870123147741360PLSCR1G/T0.240.0090.72IAUC549.20618.96758.404.0 × 10−4
rs8376783191168575LEPREL1C/T0.230.0071.39Fasting glucose2.792.823.020.008
rs10517351435352269A/G0.830.0100.71ISI0.410.470.590.010
rs41288794162098442A/G0.850.0070.67ISI1.460.620.520.009
rs10521005533638471ADAMTS1C/T0.460.0040.74IAUC659.01568.57550.300.007
rs9292501533639167ADAMTS1+A/G0.450.0050.75GAUC201.46197.18186.880.006
IAUC655.02570.18550.120.008
rs9292502533639516ADAMTS1+A/G0.460.0030.74GAUC201.78197.24186.940.006
IAUC661.14571.39551.030.006
rs709668596199942C/T0.280.0090.73GAUC201.47191.03183.010.002
rs9506645103381835+C/T0.620.0091.35GAUC188.26190.43205.911.4 × 10−4
rs9901335108073268+C/T0.860.0041.58GAUC169.38189.40197.900.006
rs77208355117269389+C/T0.200.0061.41HOMA-IR2.262.483.250.002
rs43658695117282887A/T0.790.0090.72HOMA-IR3.242.462.270.003
rs14230035147427736SPINK5A/G0.450.0041.38HOMA-IR2.512.322.120.008
rs18624465147460749SPINK5+A/C0.450.0061.37HOMA-IR2.502.322.120.009
rs14229305167330171ODZ2+C/T0.090.0030.52HOMA-IR2.272.721.450.002
rs777079766566961LY86C/T0.430.0050.73IAUC536.16579.90649.950.010
rs104849086108410287+C/G0.110.0091.53GAUC192.64207.68212.030.001
rs1023770178860569+C/T0.450.0091.33ISI0.670.490.510.008
rs10487563748905713C/T0.230.0020.68ISI0.490.600.801.4 × 10−4
rs2237457750693638Grb10A/G0.631.1 × 10−50.61GAUC214.90197.81191.930.001
rs10499761756161137LOC650200A/G0.750.0071.42GAUC178.50192.32201.720.001
rs3753107791467087AKAP9C/T0.770.0060.72HOMA-IR2.882.502.270.007
rs10488510791498161AKAP9+G/T0.230.0061.39HOMA-IR2.292.542.760.010
rs6470557114159262A/G0.250.0071.41IAUC551.83620.21780.973.8 × 10−4
ISI0.490.650.680.001
rs104882847119742580KCND2A/G0.150.0010.60HOMA-IR2.492.142.530.003
rs192392853094411+A/C0.540.0040.74IAUC650.81600.14540.140.007
rs2450148853112873C/T0.470.0101.31IAUC537.54580.77669.940.002
rs10504133853152586+C/T0.510.0020.72IAUC659.06595.05525.290.001
rs70016458105192526RIMS2+C/G0.440.0071.34ISI0.630.530.460.008
rs92973578106211509A/G0.230.0060.68GAUC201.81185.25199.130.001
rs105052298115908561+C/T0.180.0021.50GAUC193.84200.43230.740.004
rs10511574911941204+A/C0.090.0021.82GAUC193.05209.84170.350.007
rs10511777926773463A/G0.940.0060.53Fasting glucose3.192.922.800.002
rs10491665929401568+A/C0.090.0060.58GAUC198.29185.73171.340.007
rs28044981033660713NRP1A/G0.400.0011.42Fasting glucose2.782.822.890.003
rs7686761044022687+A/T0.890.0020.61Fasting glucose3.002.892.803.9 × 10−4
rs11118031072426094+C/T0.550.0080.75GAUC208.11193.50191.120.004
rs24378711090268360C10orf5+A/C0.540.0030.72ISI0.470.510.680.001
rs105095891091804145A/C0.110.0041.61HOMA-IR2.342.742.510.010
rs188797910110133240+A/T0.410.0090.74GAUC201.35193.00187.750.010
rs10500651115530156+G/T0.730.0061.42HOMA-IR2.882.462.270.005
rs711981411107941856EXPH5+C/T0.140.0071.50ISI0.580.460.290.008
rs105061731239431860CNTN1+A/G0.950.0070.55Fasting glucose2.972.912.810.007
rs3122721239534200CNTN1+C/T0.690.0071.37Fasting glucose2.772.782.860.002
rs1928521239537359CNTN1C/T0.320.0090.74Fasting glucose2.862.772.770.001
rs22895221239616798CNTN1+C/T0.550.0011.46Fasting glucose2.762.812.860.004
rs37942471239646028CNTN1+A/C0.570.0021.42Fasting glucose2.762.812.860.003
rs105212101712966928+C/T0.650.0091.34GAUC184.59193.63199.650.009
rs99152201713630703+A/G0.950.0012.72Fasting glucose2.692.732.830.009
rs5302051842639148+C/T0.610.0090.76IAUC642.24605.90538.520.008
rs29532711847696031A/T0.380.0020.69GAUC200.87195.67183.770.004
rs105029711849141959DCC+A/G0.590.0091.34GAUC186.36193.47203.520.001
rs6156961849946910MBD2+C/T0.790.0060.69Fasting glucose2.892.842.780.010
rs7394531940771776+A/G0.600.0050.73IAUC685.23586.92536.510.002
rs37457181953406965CARD8A/G0.400.0100.75GAUC202.60193.05186.480.003
rs297765204435111+A/G0.672.1 × 10−41.55Fasting glucose2.742.802.850.004
GAUC186.37191.30203.120.001
rs22551402131975858SFRS15+C/T0.870.0091.57ISI0.370.480.600.004
  • SNPs with P < 0.01 for type 2 diabetes associations were tested for consistency in a sample of nondiabetic individuals (295 of whom overlapped with the type 2 diabetes association dataset). Direction of association for glucose traits was required to be higher for diabetes risk allele. Neighboring SNPs in bold are in high LD (r2 > 0.80).

  • *

    * Genic region that contains associated SNPs.

  • P values derived using the additive genetic model, adjusted for age, sex, and family structure. The complete dataset including results for dominant and recessive models are available online (available at http://www.medschool.umaryland.edu/amishstudies/index.asp).

  • §

    § OR calculated from a liability threshold model for allele 2 versus allele 1.

  • Mean values for traits are presented by genotype, with alleles shown in alphabetical order as “1/2.” All insulin traits (IAUC, HOMA-IR, and ISI) were natural log transformed prior to analysis.