Table 2.
Top signals (PJOINT<5×10−6) from the 2 degree-of-freedom test with the MTNR1B SNP rs10830963 interaction effect and the marginal SNP effect regressed on T2D risk in pooled analysis of ARIC, CARDIA, JHS, MESA, and WFSM African American cases with type 2 diabetes and controls.
| SNPa (Nearest Gene) | Chr | Positionb | SNP Function | MAFc | βMAIN (SEMAIN)d | βINTXN (SEINTXN)e | PINTXNf | PJOINTf | PINTXN_ADJ_BMIg | PJOINT_ADJ_BMIg |
|---|---|---|---|---|---|---|---|---|---|---|
| rs7903146 (TCF7L2) | 10 | 114758349 | intronic | 0.30 | 0.29 (0.05) | 0.14 (0.14) | 3.09E-01 | 5.47E-11 | 6.23E-01 | 1.44E-10 |
| rs34872471 (TCF7L2) | 10 | 114754071 | intronic | 0.35 | 0.25 (0.05) | 0.00 (0.13) | 9.94E-01 | 3.36E-08 | 6.35E-01 | 3.15E-08 |
| rs17197883 (CMIP) | 16 | 81523013 | intronic | 0.11 | −0.24 (0.08) | 1.12 (0.20) | 1.43E-08 | 4.70E-08 | 2.53E-07 | 8.91E-07 |
| rs35198068 (TCF7L2) | 10 | 114754784 | intronic | 0.36 | 0.25 (0.05) | 0.00 (0.13) | 9.77E-01 | 5.88E-08 | 5.99E-01 | 5.72E-08 |
| rs2836995 (WRB) | 21 | 40748801 | intergenic | 0.49 | 0.00 (0.04) | −0.58 (0.11) | 3.49E-07 | 2.97E-07 | 2.70E-06 | 8.43E-07 |
| rs11819613 (TCF7L2) | 10 | 114746717 | intronic | 0.11 | 0.36 (0.07) | −0.24 (0.20) | 2.30E-01 | 3.28E-07 | 1.00E-01 | 8.46E-07 |
| rs4818031 (WRB) | 21 | 40747523 | intergenic | 0.37 | −0.01 (0.05) | −0.60 (0.12) | 5.23E-07 | 3.31E-07 | 2.83E-06 | 5.24E-07 |
| rs4818032 (WRB) | 21 | 40747583 | intergenic | 0.36 | 0.00 (0.05) | −0.61 (0.12) | 3.03E-07 | 3.52E-07 | 1.34E-06 | 5.97E-07 |
| rs2836994 (WRB) | 21 | 40748006 | intergenic | 0.48 | −0.01 (0.04) | −0.58 (0.12) | 5.61E-07 | 3.72E-07 | 5.64E-06 | 1.09E-06 |
| rs4818033 (WRB) | 21 | 40747624 | intergenic | 0.48 | −0.01 (0.04) | −0.58 (0.12) | 5.61E-07 | 3.92E-07 | 5.60E-06 | 1.15E-06 |
| rs13230 (WRB) | 21 | 40769290 | untranslated-3' | 0.45 | −0.01 (0.04) | 0.60 (0.12) | 3.68E-07 | 5.25E-07 | 8.07E-07 | 1.39E-06 |
| rs56140527 (CMIP) | 16 | 81515361 | intronic | 0.12 | −0.23 (0.07) | 0.94 (0.18) | 2.64E-07 | 5.41E-07 | 1.57E-06 | 4.01E-06 |
| rs7069007 (TCF7L2) | 10 | 114756285 | intronic | 0.11 | 0.34 (0.07) | −0.16 (0.19) | 3.99E-01 | 7.81E-07 | 1.95E-01 | 1.84E-06 |
| rs56155262 (CMIP) | 16 | 81511653 | intronic | 0.12 | −0.25 (0.07) | 0.90 (0.18) | 6.73E-07 | 8.29E-07 | 3.31E-06 | 5.52E-06 |
| rs61329995 (TCF7L2) | 10 | 114748105 | intronic | 0.11 | 0.35 (0.07) | −0.21 (0.20) | 2.78E-01 | 8.61E-07 | 1.25E-01 | 2.18E-06 |
| rs79029870 (---) | 2 | 35998316 | intergenic | 0.11 | 0.34 (0.07) | 0.10 (0.20) | 6.28E-01 | 1.10E-06 | 5.43E-01 | 1.34E-06 |
| rs116123815 (C2orf65) | 2 | 74873329 | intronic | 0.05 | 0.13 (0.10) | −1.49 (0.29) | 2.05E-07 | 1.33E-06 | 2.22E-06 | 1.23E-05 |
| rs116472028 (C2orf65) | 2 | 74872566 | intronic | 0.05 | 0.13 (0.10) | −1.49 (0.29) | 2.05E-07 | 1.33E-06 | 2.22E-06 | 1.23E-05 |
| rs73364034 (WRB) | 21 | 40744651 | intergenic | 0.36 | 0.01 (0.05) | −0.59 (0.12) | 8.20E-07 | 1.37E-06 | 2.83E-06 | 1.89E-06 |
| rs8131718 (WRB) | 21 | 40766181 | intronic | 0.45 | −0.01 (0.04) | 0.59 (0.12) | 6.77E-07 | 1.41E-06 | 1.61E-06 | 3.97E-06 |
| rs73659516 (AK128880) | 8 | 2587387 | intergenic | 0.14 | −0.08 (0.07) | −0.90 (0.20) | 1.16E-05 | 1.48E-06 | 7.05E-06 | 7.63E-07 |
| rs10438632 (CMIP) | 16 | 81510920 | intronic | 0.12 | −0.24 (0.07) | 0.88 (0.18) | 1.20E-06 | 1.55E-06 | 5.38E-06 | 9.35E-06 |
| rs73659517 (AK128880) | 8 | 2587464 | intergenic | 0.16 | −0.07 (0.07) | −0.88 (0.20) | 8.99E-06 | 1.86E-06 | 7.20E-06 | 1.20E-06 |
| rs2924879 (CSMD1) | 8 | 2702216 | intergenic | 0.39 | 0.02 (0.05) | −0.59 (0.12) | 6.73E-07 | 1.87E-06 | 4.43E-06 | 1.33E-05 |
| rs6043626 (MACROD2) | 20 | 15916192 | intronic | 0.45 | 0.18 (0.04) | 0.17 (0.12) | 1.42E-01 | 1.93E-06 | 3.30E-01 | 9.55E-06 |
| rs4319449 (TCF7L2) | 10 | 114769406 | intronic | 0.09 | 0.38 (0.08) | −0.10 (0.22) | 6.31E-01 | 2.10E-06 | 3.48E-01 | 4.13E-06 |
| rs1369455 (YTHDF3) | 8 | 64082963 | intergenic | 0.07 | −0.37 (0.09) | −0.28 (0.22) | 2.07E-01 | 2.17E-06 | 2.40E-01 | 2.25E-05 |
| rs2043525 (YTHDF3) | 8 | 64107847 | intergenic | 0.07 | −0.37 (0.09) | −0.26 (0.22) | 2.40E-01 | 2.25E-06 | 2.72E-01 | 2.37E-05 |
| rs10866267 (LOC728175) | 4 | 185239161 | near-gene-5' | 0.36 | −0.12 (0.05) | −0.42 (0.13) | 9.05E-04 | 2.27E-06 | 3.86E-03 | 6.87E-06 |
| rs9842579 (NAALADL2) | 3 | 174700592 | intronic | 0.19 | 0.29 (0.06) | −0.15 (0.17) | 3.59E-01 | 2.33E-06 | 2.88E-01 | 5.99E-07 |
| rs812665 (LOC728175) | 4 | 185245310 | intergenic | 0.34 | −0.11 (0.05) | −0.41 (0.12) | 7.08E-04 | 2.39E-06 | 1.90E-03 | 6.24E-06 |
| rs2836997 (WRB) | 21 | 40751811 | near-gene-5' | 0.49 | −0.02 (0.04) | −0.55 (0.12) | 5.11E-06 | 2.56E-06 | 2.34E-05 | 4.12E-06 |
| rs1807685 (CRYBB2) | 22 | 25639858 | intergenic | 0.23 | 0.28 (0.06) | −0.40 (0.15) | 9.40E-03 | 2.81E-06 | 5.68E-03 | 1.21E-06 |
| rs115597883 (SLC19A3) | 2 | 228559189 | intronic | 0.11 | 0.35 (0.07) | −0.69 (0.20) | 7.17E-04 | 2.93E-06 | 2.93E-04 | 1.77E-06 |
| rs2291268 (MMP19) | 12 | 56236043 | intergenic | 0.32 | −0.22 (0.05) | −0.15 (0.13) | 2.53E-01 | 2.96E-06 | 3.37E-01 | 1.72E-05 |
| rs1060180 (WRB) | 21 | 40769017 | untranslated-3' | 0.46 | −0.01 (0.04) | 0.57 (0.12) | 1.38E-06 | 3.03E-06 | 3.95E-06 | 9.47E-06 |
| rs1360814 (---) | 13 | 80403917 | intergenic | 0.18 | 0.24 (0.06) | 0.15 (0.15) | 3.13E-01 | 3.19E-06 | 4.28E-01 | 2.85E-06 |
| rs17017402 (---) | 2 | 36003758 | intergenic | 0.11 | 0.31 (0.07) | 0.07 (0.19) | 7.02E-01 | 3.35E-06 | 5.58E-01 | 3.49E-06 |
| rs1681087 (DNAJC14) | 12 | 56180764 | intronic | 0.26 | 0.21 (0.05) | 0.17 (0.13) | 1.85E-01 | 3.47E-06 | 2.48E-01 | 1.55E-05 |
| rs114812021 (SLC19A3) | 2 | 228559188 | intronic | 0.11 | 0.35 (0.07) | −0.68 (0.20) | 8.43E-04 | 3.53E-06 | 3.44E-04 | 2.05E-06 |
| rs9845886 (NAALADL2) | 3 | 174704267 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.23E-01 | 3.58E-06 | 1.55E-01 | 3.96E-07 |
| rs58538128 (FCGR3A) | 1 | 161520858 | near-gene-5' | 0.14 | 0.35 (0.08) | 0.08 (0.20) | 7.04E-01 | 3.59E-06 | 7.93E-01 | 3.93E-05 |
| rs2837021 (LCA5L) | 21 | 40796623 | intronic | 0.36 | −0.02 (0.05) | −0.56 (0.12) | 5.26E-06 | 3.60E-06 | 3.02E-06 | 2.86E-06 |
| rs4739079 (YTHDF3) | 8 | 64200821 | intergenic | 0.09 | 0.35 (0.08) | 0.08 (0.19) | 6.62E-01 | 3.72E-06 | 8.58E-01 | 1.27E-05 |
| rs59246912 (NAALADL2) | 3 | 174704393 | intronic | 0.26 | 0.24 (0.05) | −0.16 (0.14) | 2.27E-01 | 3.82E-06 | 1.57E-01 | 4.14E-07 |
| rs9862955 (NAALADL2) | 3 | 174703978 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.26E-01 | 3.88E-06 | 1.57E-01 | 4.22E-07 |
| rs9862818 (NAALADL2) | 3 | 174703904 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.26E-01 | 3.88E-06 | 1.57E-01 | 4.20E-07 |
| rs16846841 (HECW2) | 2 | 197063250 | intergenic | 0.20 | 0.06 (0.06) | −0.81 (0.16) | 6.80E-07 | 3.89E-06 | 2.22E-06 | 1.09E-05 |
| rs9862801 (NAALADL2) | 3 | 174703876 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.26E-01 | 3.90E-06 | 1.57E-01 | 4.25E-07 |
| rs7228666 (SLMO1) | 18 | 12427118 | intronic | 0.23 | −0.17 (0.05) | 0.68 (0.14) | 1.77E-06 | 3.93E-06 | 4.21E-06 | 8.64E-06 |
| rs9821147 (NAALADL2) | 3 | 174703737 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.26E-01 | 3.94E-06 | 1.57E-01 | 4.31E-07 |
| rs13323013 (NAALADL2) | 3 | 174703232 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.26E-01 | 4.07E-06 | 1.57E-01 | 4.50E-07 |
| rs1335279 (---) | 13 | 80399950 | intergenic | 0.21 | 0.21 (0.05) | 0.23 (0.15) | 1.21E-01 | 4.10E-06 | 1.73E-01 | 1.04E-05 |
| rs56864167 (---) | 2 | 35969614 | intergenic | 0.11 | 0.31 (0.07) | 0.07 (0.19) | 7.12E-01 | 4.10E-06 | 5.87E-01 | 4.52E-06 |
| rs9820271 (NAALADL2) | 3 | 174703026 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.25E-01 | 4.13E-06 | 1.56E-01 | 4.59E-07 |
| rs10412272 (USP29) | 19 | 57597884 | intergenic | 0.05 | 0.45 (0.10) | 0.14 (0.27) | 5.87E-01 | 4.34E-06 | 7.59E-01 | 6.81E-06 |
| rs2223028 (LCA5L) | 21 | 40810373 | intronic | 0.34 | 0.01 (0.05) | −0.60 (0.13) | 2.26E-06 | 4.44E-06 | 1.01E-06 | 2.16E-06 |
| rs7016339 (YTHDF3) | 8 | 64121730 | intergenic | 0.07 | −0.36 (0.09) | −0.30 (0.23) | 1.91E-01 | 4.48E-06 | 2.25E-01 | 4.53E-05 |
| rs76240879 (NAALADL2) | 3 | 174704464 | intronic | 0.26 | 0.24 (0.05) | −0.17 (0.14) | 2.25E-01 | 4.50E-06 | 1.55E-01 | 4.49E-07 |
| rs9810343 (NAALADL2) | 3 | 174701501 | intronic | 0.26 | 0.24 (0.05) | −0.18 (0.14) | 1.94E-01 | 4.60E-06 | 1.33E-01 | 5.23E-07 |
| rs6735529 (LINC00299) | 2 | 8614384 | intergenic | 0.05 | 0.23 (0.10) | 0.78 (0.24) | 1.41E-03 | 4.67E-06 | 5.54E-03 | 2.97E-05 |
| rs16870669 (RIMS2) | 8 | 104773461 | intronic | 0.11 | 0.22 (0.07) | 0.47 (0.19) | 1.41E-02 | 4.98E-06 | 2.82E-02 | 1.30E-06 |
a
SNP interacting with rs10830963.
b
NCBI build 37.
c
Minor allele frequency.
d
Marginal genetic effect from interaction models adjusted for age, gender, and PC1.
e
Interaction effect from interaction models adjusted for age, gender, and PC1.
f
Interaction and joint p-values from interaction models adjusted for age, gender, and PC1.
g
Interaction and joint p-values from interaction models adjusted for age, gender, PC1, and BMI.