TABLE 1

Association of SNPs in/near CDKAL1, SLC30A8, HHEX, EXT2, IGF2BP2, CDKN2B, LOC387761, and FTO with type 2 diabetes and BMI in a population-based sample of full-heritage Pima Indians

SNPGeneChromosomeAllele 1/2A. 2. FrequencySubjects by genotype with type 2 diabetes (top row) and nondiabetic subjects (bottom row)
BMI by genotype (top row) and number of subjects (bottom row)
Additive P value
1/11/22/2Additive P valueAdditive OR (95% CI)1/11/22/2
rs6935317CDKAL16C/T0.25763532830.700.97 (0.85–1.12)35.9 ± 8.136.6 ± 8.436.3 ± 8.80.13
0.241,0016501041,429950143
rs1569660CDKAL16A/G0.296985561140.880.99 (0.87–1.13)36.0 ± 8.136.4 ± 8.336.2 ± 8.40.34
0.288927201341,2901,022196
rs2328528CDKAL16A/T0.23874474980.390.94 (0.81–1.08)36.4 ± 8.435.9 ± 7.835.9 ± 7.60.13
0.221,095623761,605873135
rs7754840*CDKAL16G/C0.287504951320.381.06 (0.93–1.22)36.6 ± 8.635.9 ± 7.935.1 ± 7.10.01
0.269596601161,379937189
rs7756992*CDKAL16A/G0.346105741780.151.10 (0.97–1.25)36.5 ± 8.636.1 ± 7.835.5 ± 7.80.09
0.328207441841,1531,072280
rs9295479CDKAL16T/A0.444487342660.571.03 (0.92–1.16)36.0 ± 8.136.2 ± 8.036.6 ± 8.60.31
0.445688623668091,273531
rs4351239CDKAL16T/C0.121,068287170.111.16 (0.97–1.39)36.2 ± 8.236.3 ± 8.236.3 ± 7.80.98
0.141,303409331,90356541
rs1004172CDKAL16C/T0.20874418610.181.10 (0.96–1.27)36.0 ± 8.336.7 ± 8.136.0 ± 8.20.32
0.211,078579791,585798104
rs1498426CDKAL16T/C0.248404611010.160.91 (0.79–1.04)36.5 ± 8.135.7 ± 8.236.7 ± 8.70.05
0.221,063604821,552851132
rs9465946CDKAL16A/G0.18969392590.110.88 (0.76–1.03)36.4 ± 8.135.9 ± 8.437.6 ± 8.90.41
0.171,233507461,79170678
rs10946425CDKAL16C/T0.18909416430.161.12 (0.96–1.31)36.3 ± 8.235.9 ± 8.236.4 ± 8.30.49
0.191,151519801,66075199
rs9465948CDKAL16G/A0.031,2898810.320.84 (0.60–1.19)36.2 ± 8.236.0 ± 8.838.20.73
0.031,64011802,3701521
rs9295488CDKAL16G/A0.415156592520.710.98 (0.86–1.10)36.2 ± 8.236.3 ± 8.236.2 ± 8.20.40
0.396478442749401,220410
rs4712580CDKAL16C/T0.17995361540.490.94 (0.80–1.11)36.3 ± 8.136.2 ± 8.236.2 ± 8.90.13
0.151,284453421,84965370
rs9295491CDKAL16G/T0.395206452090.840.99 (0.88–1.11)36.1 ± 8.336.1 ± 8.036.7 ± 8.60.69
0.387118032721,0221,160380
rs6456396CDKAL16G/C0.041,22411510.851.03 (0.76–1.39)36.2 ± 8.235.1 ± 8.036.9 ± 6.10.03
0.051,52715832,2172124
rs4076112CDKAL16A/G0.021,3976210.611.10 (0.75–1.61)36.2 ± 8.235.6 ± 8.4NA0.28
0.031,7189102,5161180
rs12055489CDKAL16A/G0.17938391380.811.02 (0.86–1.21)36.2 ± 8.236.2 ± 8.237.2 ± 7.50.53
0.171,211481521,73568879
rs9295496CDKAL16A/G0.021,3815610.661.10 (0.73–1.63)36.2 ± 8.235.6 ± 8.134.20.33
0.021,7007712,4891001
rs9295497CDKAL16G/A0.021,3825310.771.07 (0.69–1.65)36.2 ± 8.236.7 ± 7.6NA0.66
0.021,6906602,482900
rs9465982CDKAL16C/T0.18893401420.831.02 (0.87–1.19)36.4 ± 8.135.9 ± 8.535.2 ± 6.60.05
0.181,145508551,64473970
rs9295501CDKAL16A/G0.0011,363200.770.80 (0.18–3.52)36.2 ± 8.235.1 ± 10.6NA0.77
0.0011,741302,49930
rs12527222CDKAL16C/T0.021,3305010.741.08 (0.70–1.66)36.2 ± 8.237.0 ± 7.6NA0.42
0.021,6706402,415890
rs898165CDKAL16C/T0.161,029382370.630.96 (0.81–1.13)36.1 ± 8.036.6 ± 8.635.8 ± 8.20.62
0.141,310442321,89765452
rs4710965CDKAL16G/C0.081,221204160.231.14 (0.92–1.42)36.3 ± 8.235.7 ± 8.434.8 ± 6.30.03
0.101,485312242,17242133
rs6937610CDKAL16A/G0.326216181330.471.05 (0.92–1.20)36.5 ± 8.236.0 ± 8.235.9 ± 7.90.26
0.357447542221,0731,122292
rs9460612CDKAL16G/A0.414716592330.460.95 (0.84–1.08)36.2 ± 8.336.0 ± 8.236.9 ± 7.90.25
0.406008782528681,246373
rs7002176SLC30A88T/A0.25756500840.340.93 (0.81–1.08)36.3 ± 8.236.1 ± 8.135.6 ± 7.80.16
0.24977599961,404876146
rs13266634*SLC30A88C/T0.091,156209160.711.04 (0.84–1.29)36.1 ± 8.236.5 ± 8.536.9 ± 8.00.98
0.091,455296152,09540924
rs1995222SLC30A88G/A0.131,038320220.421.07 (0.90–1.27)36.2 ± 8.236.4 ± 8.335.4 ± 8.30.38
0.151,307433431,84561356
rs1111875*HHEX10T/C0.404996612140.511.04 (0.92–1.18)36.3 ± 8.136.1 ± 8.136.6 ± 8.80.86
0.386598412489231,223366
rs10509646HHEX10T/C0.464146802910.021.15 (1.02–1.29)36.1 ± 8.336.3 ± 8.236.2 ± 8.40.90
0.494678794186941,271568
rs3740878*EXT211G/A0.131,037315160.571.05 (0.88–1.27)36.1 ± 8.136.5 ± 8.535.4 ± 8.80.53
0.131,324384341,89756442
rs6777038IGF2BP23C/T0.021,3284820.191.31 (0.88–1.96)36.2 ± 8.236.3 ± 7.946.20.94
0.031,6729002,4211061
rs16860234IGF2BP23A/C0.061,19915640.740.96 (0.74–1.23)36.1 ± 8.336.7 ± 7.937.4 ± 7.50.54
0.061,52518972,2072618
rs4402960*§IGF2BP23G/T0.17942370410.321.08 (0.93–1.26)36.3 ± 8.235.9 ± 8.235.6 ± 7.30.14
0.171,186461541,73565670
rs10811661*CDKN2B9T/C0.061,21414930.381.13 (0.86–1.49)36.1 ± 8.237.3 ± 8.636.2 ± 6.60.08
0.061,54420432,2112946
rs7480010*LOC38776111A/G0.16976368330.751.03 (0.86–1.22)36.1 ± 8.236.6 ± 8.337.0 ± 9.40.35
0.141,302418401,82763956
rs8050136*FTO16C/A0.151,071357440.031.20 (1.02–1.41)36.1 ± 8.236.7 ± 8.037.7 ± 8.30.002
0.141,360435301,97562455
  • Data are n or means ± SD unless otherwise indicated.

  • *

    * SNP previously reported to be associated with type 2 diabetes in a Caucasian GWA study (26). For SNPs determined to be in complete linkage disequilibrium (D′ ≥ 0.99), only one representative SNP is shown.

  • rs7754840 (shown) is in complete linkage disequilibrium with rs10946398 and rs4712523 (not shown).

  • rs3740878 (shown) is in linkage disequilibrium with rs1113132 (not shown).

  • §

    § rs4402960 (shown) is in linkage disequilibrium with rs1470579 (not shown).

  • rs8050136 is in linkage disequilibrium with rs9939609 and rs7193144 (not shown). Data for monomophic SNPs rs9300039 and rs17738231 are not shown. P values were adjusted for age, sex, and birth year. ORs for type 2 diabetes are expressed per copy of the underlined allele; for previously reported variants, this is the risk allele identified in Europeans (27), whereas for other variants it is arbitrarily set as allele 1 (major allele). BMI for these longitudinally studied subjects is defined as the maximum BMI recorded from a nondiabetic exam. In addition to the general analysis shown in the table, all variants were analyzed using a within-family analysis. With the exception of variants in FTO (detailed in Table 3), no variant showed a significant association (P < 0.05) with either type 2 diabetes or BMI using a within-family analysis. NA, analytical model not applicable due to low frequency.