Introduction
Methods
Study participants
SNP selection
Genotyping
Association analysis
Haplotype association analysis
Locus-specific gout genetic risk score
Results
Allelic associations
East Polynesian (EP) (High) | East Polynesian (Low) | West Polynesian (WP) | East/West Polynesian | European Caucasian | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SNPb | Chr:Posc | Effect/Otherd | Allele Freq. | ORe(95% CI) |
P
e
| Allele Freq. | ORe(95% CI) |
P
e
| Allele Freq. | ORe(95% CI) |
P
e
| Allele Freq. | ORe(95% CI) |
P
e
| Allele Freq. | ORe(95% CI) |
P
e
| ||||||
Case | Con | Case | Con | Case | Con | Case | Con | Case | Con | ||||||||||||||
1a | T/C | 0.571 | 0.531 | 1.19 | 0.257 | 0.566 | 0.601 | 1.01 | 0.957 | 0.403 | 0.409 | 1.06 | 0.758 | 0.500 | 0.400 | 1.65 | 0.412 | 0.566 | 0.564 | 1.02 | 0.868 | ||
(0.88,1.61) | (0.63,1.64) | (0.75,1.49) | (0.50,5.48) | (0.84,1.24) | |||||||||||||||||||
1 | rs17299124 | 11:64256859 | C/A | 0.976 | 0.950 | 2.77 | 0.019 | 0.821 | 0.801 | 1.20 | 0.577 | 0.994 | 0.957 | 5.65 | 0.011 | 0.974 | 0.947 | 3.00 | 0.461 | 0.733 | 0.752 | 0.91 | 0.401 |
(1.18,6.50) | (0.63,2.32) | (1.49,21.39) | (0.16,55.71) | (0.73,1.14) | |||||||||||||||||||
2 | rs693591 | 11:64325069 | C/G | 0.522 | 0.449 | 1.41 | 0.031 | 0.315 | 0.291 | 1.13 | 0.630 | 0.373 | 0.367 | 1.00 | 0.992 | 0.526 | 0.260 | 4.55 | 0.025 | 0.139 | 0.135 | 0.95 | 0.733 |
(1.03,1.92) | (0.68,1.89) | (0.72,1.40) | (1.21,17.06) | (0.72-1.26) | |||||||||||||||||||
2 | rs17300741 | 11:64331462 | A/G | 0.819 | 0.789 | 1.30 | 0.187 | 0.604 | 0.557 | 1.29 | 0.312 | 0.808 | 0.830 | 0.76 | 0.213 | 0.806 | 0.750 | 1.42 | 0.595 | 0.476 | 0.439 | 1.05 | 0.611 |
(0.88,1.91) | (0.78,2.14) | (0.49,1.17) | (0.39,5.24) | (0.87,1.27) | |||||||||||||||||||
2 | rs2078267 | 11:64334114 | C/T | 0.938 | 0.910 | 1.78 | 0.063 | 0.651 | 0.606 | 1.19 | 0.526 | 0.980 | 0.944 | 2.20 | 0.071 | 0.921 | 0.886 | 1.21 | 0.815 | 0.479 | 0.456 | 0.98 | 0.816 |
(0.97,3.26) | (0.70,2.00) | (0.94,5.17) | (0.24,6.11) | ([0.81,1.18] | |||||||||||||||||||
3 | rs3825018 | 11:64358809 | G/A | 0.739 | 0.674 | 1.46 | 0.028 | 0.500 | 0.447 | 1.37 | 0.206 | 0.726 | 0.712 | 1.16 | 0.404 | 0.842 | 0.660 | 1.83 | 0.316 | 0.305 | 0.267 | 1.22 | 0.065 |
(1.04,2.06)] | (0.84,2.23) | (0.82,1.66) | (0.56,5.98) | (0.99,1.50) | |||||||||||||||||||
3 | rs475688 | 11:64364291 | T/C | 0.433 | 0.427 | 1.10 | 0.543 | 0.370 | 0.295 | 1.66 | 0.073 | 0.409 | 0.461 | 0.78 | 0.145 | 0.556 | 0.420 | 1.72 | 0.391 | 0.269 | 0.236 | 1.26 | 0.043 |
(0.80,1.52) | (0.95,2.89) | (0.56,1.09) | (0.50,5.97) | ([1.01,1.57) | |||||||||||||||||||
3 | rs7932775 | 11:64367862 | C/T | 0.496 | 0.478 | 1.03 | 0.866 | 0.373 | 0.320 | 1.36 | 0.278 | 0.489 | 0.415 | 1.49 | 0.019 | 0.500 | 0.396 | 1.00 | 1.000 | 0.213 | 0.174 | 1.32 | 0.033 |
(0.76,1.40) | (0.78,2.35) | (1.07,2.09) | (0.35,2.90) | (1.02,1.69) | |||||||||||||||||||
3 | rs476037 | 11:64369540 | A/G | 0.254 | 0.206 | 1.56 | 0.022 | 0.149 | 0.136 | 1.10 | 0.787 | 0.250 | 0.303 | 0.78 | 0.165 | 0.368 | 0.250 | 2.58 | 0.161 | 0.088 | 0.089 | 1.03 | 0.846 |
(1.07,2.28) | (0.56,2.16) | (0.55,1.11) | (0.69,9.68) | (0.74,1.43) | |||||||||||||||||||
3 | rs478607 | 11:64478063 | G/A | 0.241 | 0.268 | 0.85 | 0.359 | 0.279 | 0.184 | 1.72 | 0.080 | 0.196 | 0.166 | 1.48 | 0.085 | 0.211 | 0.225 | 0.82 | 0.766 | 0.167 | 0.144 | 1.27 | 0.077 |
(0.60,1.20) | (0.94,3.15) | (0.95,2.31) | (0.23,2.98) | (0.98,1.66) | |||||||||||||||||||
4 | rs12289836 | 11:65436888 | A/G | 0.621 | 0.622 | 0.94 | 0.711 | 0.660 | 0.631 | 1.07 | 0.810 | 0.693 | 0.746 | 0.80 | 0.237 | 0.790 | 0.725 | 1.22 | 0.766 | 0.645 | 0.683 | 0.85 | 0.109 |
(0.68,1.30] | (0.62,1.85) | (0.55,1.16)] | (0.34,4.40) | (0.69,1.04) | |||||||||||||||||||
4 | rs642803 | 11:65560620 | T/C | 0.454 | 0.458 | 1.00 | 0.975 | 0.500 | 0.474 | 1.26 | 0.364 | 0.413 | 0.421 | 0.92 | 0.624 | 0.500 | 0.368 | 0.71 | 0.620 | 0.448 | 0.474 | 0.93 | 0.467 |
(0.73,1.36] | (0.77,2.07) | (0.66,1.29) | (0.18,2.75) | (0.77,1.13) |
European Caucasian and low ancestry Polynesiand | High ancestry Polynesiane | Polynesianf | All ancestriesg | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
SNP | Chr:Posb | Effect/Otherc | ORh |
P
h
| Het Ph | ORh |
P
h
| Het Ph | ORh |
P
h
| Het Ph | ORh |
P
h
| Het Ph | |
(95% CI) | (95% CI) | (95% CI) | (95% CI) | ||||||||||||
1a | rs475414 | 11:64241844 | T/C | 1.02 | 0.862 | 0.990 | 1.15 | 0.233 | 0.727 | 1.12 | 0.270 | 0.839 | 1.07 | 0.376 | 0.861 |
(0.85,1.22) | (0.92,1.43) | (0.92,1.34) | ( 0.93,1.23) | ||||||||||||
1 | rs17299124 | 11:64256859 | C/A | 0.94 | 0.539 | 0.425 | 3.38 | 6.1 × 10,4 | 0.674 | 1.95 | 0.006 | 0.153 | 1.71 | 0.109 | 0.010 |
(0.76,1.16) | (1.69,6.79) | (1.21,3.15) | ( 0.89,3.28) | ||||||||||||
2 | rs693591 | 11:64325069 | C/G | 0.99 | 0.942 | 0.559 | 1.25 | 0.051 | 0.053 | 1.23 | 0.047 | 0.113 | 1.12 | 0.167 | 0.087 |
(0.78,1.26) | (1.00,1.57) | (1.00,1.51) | ( 0.95,1.33) | ||||||||||||
2 | rs17300741 | 11:64331462 | A/G | 1.08 | 0.402 | 0.446 | 1.04 | 0.793 | 0.173 | 1.10 | 0.469 | 0.254 | 1.07 | 0.396 | 0.388 |
(0.90,1.29) | (0.78,1.38) | (0.86,1.40) | ( 0.92,1.24) | ||||||||||||
2 | rs2078267 | 11:64334114 | C/T | 1.00 | 0.999 | 0.499 | 1.84 | 0.012 | 0.804 | 1.51 | 0.022 | 0.591 | 1.08 | 0.370 | 0.169 |
(0.84,1.20) | (1.14,2.95) | (1.06,2.14) | (0.91,1.28) | ||||||||||||
3 | rs3825018 | 11:64358809 | G/A | 1.24 | 0.028 | 0.660 | 1.33 | 0.020 | 0.568 | 1.34 | 0.008 | 0.767 | 1.27 | 0.002 | 0.822 |
(1.02,1.50) | (1.05,1.69) | (1.08,1.66) | (1.10,1.48) | ||||||||||||
3 | rs475688 | 11:64364291 | T/C | 1.31 | 0.011 | 0.360 | 0.95 | 0.683 | 0.216 | 1.03 | 0.768 | 0.096 | 1.13 | 0.109 | 0.093 |
(1.06,1.60) | (0.76,1.20) | (0.84,1.27) | (0.97,1.32) | ||||||||||||
3 | rs7932775 | 11:64367862 | C/T | 1.32 | 0.017 | 0.923 | 1.21 | 0.095 | 0.256 | 1.23 | 0.051 | 0.412 | 1.26 | 0.004 | 0.550 |
(1.05,1.66) | (0.97,1.51) | (1.00,1.51) | (1.08,1.48) | ||||||||||||
3 | rs476037 | 11:64369540 | A/G | 1.05 | 0.770 | 0.874 | 1.25 | 0.480 | 0.014 | 1.19 | 0.461 | 0.036 | 1.08 | 0.423 | 0.070 |
(0.78,1.40] | (0.67,2.34) | (0.75,1.89) | (0.89,1.31) | ||||||||||||
3 | rs478607 | 11:64478063 | G/A | 1.33 | 0.020 | 0.371 | 1.04 | 0.785 | 0.148 | 1.13 | 0.337 | 0.109 | 1.19 | 0.056 | 0.167 |
(1.05,1.70) | (0.79,1.36) | (0.88,1.44) | (1.00,1.43) | ||||||||||||
4 | rs12289836 | 11:65436888 | A/G | 0.87 | 0.156 | 0.435 | 0.89 | 0.327 | 0.717 | 0.91 | 0.423 | 0.791 | 0.88 | 0.085 | 0.863 |
(0.72,1.05) | (0.70,1.13) | (0.73,1.14) | (0.76,1.02) | ||||||||||||
4 | rs642803 | 11:65560620 | T/C | 0.97 | 0.728 | 0.267 | 0.95 | 0.662 | 0.862 | 1.00 | 0.982 | 0.726 | 0.96 | 0.586 | 0.818 |
(0.81,1.16) | (0.76,1.19) | (0.81,1.23) | (0.84,1.11) |
Haplotype association analysis
European Caucasian and low ancestry Polynesianb | High ancestry Polynesianc | Polynesiand | All ancestriese | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Hap
a
| ORf | Pf | Het Pf | ORf | Pf | Het Pf | ORf | Pf | Het Pf | ORf | Pf | Het Pf |
(95% CI) | (95% CI) | (95% CI) | (95% CI) | |||||||||
Block 1 (rs475414|rs17299124) | ||||||||||||
C|C | 0.94 | 0.501 | 0.795 | 0.89 | 0.305 | 0.884 | 0.91 | 0.349 | 0.936 | 0.92 | 0.242 | 0.978 |
(0.78,1.13) | (0.71,1.11) | (0.74,1.11) | (0.80,1.06) | |||||||||
T|A | 1.07 | 0.549 | 0.379 | 0.28 | 6.0 × 10,4 | 0.512 | 0.50 | 0.006 | 0.120 | 0.56 | 0.103 | 0.007 |
(0.86,1.32) | (0.14,0.58) | (0.31,0.82) | (0.28,1.12) | |||||||||
T|C | 1.02 | 0.848 | 0.584 | 1.30 | 0.022 | 0.914 | 1.29 | 0.019 | 0.965 | 1.14 | 0.093 | 0.572 |
(0.83,1.25) | (1.04,1.63) | (1.04,1.56) | (0.98,1.33) | |||||||||
Block 2 (rs693591|rs17300741|rs2078267) | ||||||||||||
C|A|C | 0.97 | 0.800 | 0.726 | 1.24 | 0.070 | 0.128 | 1.20 | 0.083 | 0.219 | 1.10 | 0.253 | 0.179 |
(0.76,1.24) | (0.98,1.56) | (0.98,1.49) | (0.93,1.30) | |||||||||
G|A|C | 1.08 | 0.468 | 0.842 | 0.78 | 0.037 | 0.446 | 0.83 | 0.083 | 0.368 | 0.94 | 0.440 | 0.204 |
(0.88,1.31) | (0.61,0.99) | (0.67,1.03) | (0.81,1.10) | |||||||||
G|G|C | , | , | , | 1.35 | 0.093 | 0.369 | 1.31 | 0.113 | 0.509 | , | , | , |
(0.95,1.91) | (0.94,1.83) | |||||||||||
G|G|T | 0.97 | 0.706 | 0.682 | 0.57 | 0.022 | 0.797 | 0.69 | 0.042 | 0.600 | 0.91 | 0.252 | 0.316 |
(0.81,1.15) | (0.35,0.92) | (0.49,0.99) | (0.77,1.07) | |||||||||
Block 3 (rs3825018|rs475688|rs7932775|rs476037|rs478607) | ||||||||||||
A|C|T|G|A | 0.82 | 0.040 | 0.953 | 0.76 | 0.035 | 0.272 | 0.77 | 0.024 | 0.451 | 0.80 | 0.004 | 0.594 |
(0.67,0.99) | (0.59,0.98) | (0.62,0.97) | (0.68,0.93) | |||||||||
G|C|C|G|A | 1.06 | 0.816 | 0.425 | 1.31g | 0.105 | 0.969 | 1.23g | 0.183 | 0.543 | 1.22h | 0.142 | 0.746 |
(0.66,1.69) | (0.95,1.81) | (0.91,1.67) | (0.94,1.60) | |||||||||
G|C|C|G|G | , | , | , | 1.33 | 0.116 | 0.702 | 1.29 | 0.151 | 0.752 | , | , | , |
(0.93,1.90) | (0.91,1.81) | |||||||||||
G|T|C|G|A | , | , | , | 0.93 | 0.730 | 0.905 | , | , | , | , | , | , |
(0.63,1.39) | ||||||||||||
G|T|C|G|G | 1.41 | 0.007 | 0.248 | 0.63 | 0.028 | 0.821 | 0.86 | 0.690 | 0.028 | 1.01 | 0.984 | 0.014 |
(1.10,1.82) | (0.41,0.95) | (0.41,1.80) | (0.61,1.66) | |||||||||
G|T|T|A|A | 1.01 | 0.947 | 0.731 | 1.19 | 0.573 | 0.029 | 1.07 | 0.590 | 0.062 | 1.06 | 0.579 | 0.118 |
(0.87,1.29) | ||||||||||||
(0.75,1.36) | (0.66,2.14) | (0.84,1.36) |
East Polynesian (High)b | East Polynesian (Low)c | West Polynesian | East/West Polynesian | European Caucasian | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Hap
a
| Freq. | ORd(95% CI) |
P
d
| Freq. | ORd(95% CI) |
P
d
| Freq. | ORd(95% CI) |
P
d
| Freq. | ORd(95% CI) |
P
d
| Freq. | ORd(95% CI) |
P
d
| |||||
Case | Con | Case | Con | Case | Con | Case | Con | Case | Con | |||||||||||
Block 1 (rs475414|rs17299124) | ||||||||||||||||||||
C|C | 0.437 | 0.472 | 0.86 | 0.321 | 0.434 | 0.397 | 1.00 | 0.988 | 0.598 | 0.595 | 0.94 | 0.745 | 0.500 | 0.579 | 0.75 | 0.648 | 0.430 | 0.450 | 0.93 | 0.471 |
(0.63,1.16) | (0.61,1.62) | (0.67,1.34) | (0.22,2.60) | (0.76,1.14) | ||||||||||||||||
T|A | 0.024 | 0.051 | 0.35 | 0.017 | 0.179 | 0.203 | 0.81 | 0.525 | 0.004 | 0.044 | 0.12 | 0.009 | 0.026 | 0.053 | 0.33 | 0.461 | 0.262 | 0.245 | 1.10 | 0.393 |
(0.15,0.83) | (0.42,1.56) | (0.03,0.59) | (0.02,6.19) | (0.88,1.38) | ||||||||||||||||
1.34 | 0.063 | 0.387 | 0.400 | 1.18 | 0.562 | 0.396 | 0.361 | 1.24 | 0.228 | 0.474 | 0.368 | 1.53 | 0.486 | 0.302 | 0.301 | 1.00 | 0.984 | |||
T|C | 0.539 | 0.477 | (0.98,1.82) | (0.67,2.09) | (0.88,1.76) | (0.46,5.08) | (0.80,1.24) | |||||||||||||
Block 2 (rs693591|rs17300741|rs2078267) | ||||||||||||||||||||
C|A|C | 0.525 | 0.458 | 1.38 | 0.047 | 0.315 | 0.298 | 1.05 | 0.849 | 0.373 | 0.371 | 1.02 | 0.933 | 0.528 | 0.283 | 3.49 | 0.063 | 0.139 | 0.134 | 0.95 | 0.698 |
(1.00,1.90) | (0.63,1.77) | (0.72,1.43) | (0.93,13.01) | (0.72,1.25) | ||||||||||||||||
G|A|C | 0.299 | 0.350 | 0.77 | 0.136 | 0.287 | 0.272 | 1.13 | 0.654 | 0.436 | 0.461 | 0.83 | 0.288 | 0.278 | 0.478 | 0.38 | 0.106 | 0.329 | 0.302 | 1.07 | 0.543 |
(0.54,1.09) | (0.66,1.95) | (0.60,1.17) | (0.12,1.23) | (0.87,1.32) | ||||||||||||||||
G|G|C | 0.11 | 0.102 | 1.09 | 0.734 | 0.046 | 0.040 | 0.94 | 0.914 | 0.17 | 0.121 | 1.72 | 0.032 | 0.111 | 0.13 | 0.76 | 0.758 | , | , | , | , |
(0.66,1.83) | (0.28,3.14) | (1.05,2.83) | (0.14,4.30) | |||||||||||||||||
G|G|T | 0.061 | 0.090 | 0.56 | 0.070 | 0.352 | 0.381 | 0.87 | 0.607 | 0.019 | 0.043 | 0.50 | 0.117 | 0.083 | 0.109 | 0.93 | 0.932 | 0.525 | 0.556 | 0.98 | 0.830 |
(0.30,1.05) | (0.52,1.47) | (0.21,1.19) | (0.19,4.68) | (0.81,1.18) | ||||||||||||||||
Block 3 (rs3825018|rs475688|rs7932775|rs476037|rs478607) | ||||||||||||||||||||
A|C|T|G|A | 0.273 | 0.327 | 0.71 | 0.053 | 0.510 | 0.545 | 0.81 | 0.420 | 0.290 | 0.303 | 0.89 | 0.520 | 0.167 | 0.421 | 0.29 | 0.088 | 0.678 | 0.717 | 0.82 | 0.059 |
(0.50,1.01) | (0.48,1.36) | (0.61,1.28) | (0.07,1.21) | (0.67,1.01) | ||||||||||||||||
G|C|C|G|A | 0.179 | 0.136 | 1.26 | 0.283 | 0.078 | 0.115 | 0.78 | 0.582 | 0.159 | 0.129 | 1.37 | 0.214 | 0.139 | 0.053 | , | 0.997 | 0.035 | 0.024 | 1.19 | 0.534 |
(0.83,1.93) | (0.32,1.88) | (0.83,2.26) | (0.68,2.08) | |||||||||||||||||
G|C|C|G|G | 0.116 | 0.108 | 1.14 | 0.599 | 0.039 | 0.038 | 0.82 | 0.767 | 0.142 | 0.114 | 1.54 | 0.100 | 0.111 | 0.105 | 1.71 | 0.659 | , | , | , | , |
(0.69,1.89) | (0.23,2.98) | (0.92,2.59) | (0.16,18.73) | |||||||||||||||||
G|T|C|G|A | 0.057 | 0.068 | 0.84 | 0.574 | 0.000 | 0.016 | , | 0.998 | 0.111 | 0.102 | 1.01 | 0.971 | 0.139 | 0.053 | 0.96 | 0.968 | , | , | , | , |
(0.46,1.55) | (0.59,1.73) | (0.14,6.67) | ||||||||||||||||||
G|T|C|G|G | 0.098 | 0.139 | 0.64 | 0.068 | 0.226 | 0.131 | 2.03 | 0.036 | 0.026 | 0.034 | 0.63 | 0.354 | 0.056 | 0.105 | 0.31 | 0.301 | 0.161 | 0.133 | 1.33 | 0.039 |
(0.40,1.03) | (1.05,3.95) | (0.24,1.68) | (0.04,2.83) | (1.01,1.75) | ||||||||||||||||
G|T|T|A|A | 0.266 | 0.213 | 1.53 | 0.030 | 0.128 | 0.131 | 0.90 | 0.776 | 0.264 | 0.314 | 0.78 | 0.183 | 0.361 | 0.263 | 2.28 | 0.300 | 0.088 | 0.087 | 1.04 | 0.836 |
(1.04,2.24) | (0.44,1.85) | (0.55,1.12) | (0.48,10.80) | (0.74,1.44) |
Gout genetic risk-score association
Mean ± standard deviation | ū1-ū2a |
t
a
|
P
a
| ORb |
P
b
| Variance explained (%)c | ||
---|---|---|---|---|---|---|---|---|
Case | Control | (95% CI)a | (95% CI) | |||||
East Polynesian (H) | 10.93 ± 1.56 | 10.45 ± 1.91 | 0.48 | 2.71 | 0.007 | 1.22 | 0.002 | 1.38 |
(0.13, 0.83) | (1.07-1.39) | |||||||
East Polynesian (L) | 4.81 ± 1.70 | 4.68 ± 1.96 | 0.13 | 0.47 | 0.64 | 1.03 | 0.77 | 0.09 |
(-0.44, 0.71) | (0.84-1.26) | |||||||
West Polynesian | 17.24 ± 1.21 | 16.57 ± 2.95 | 0.67 | 2.43 | 0.016 | 1.14 | 0.041 | 1.89 |
(0.13, 1.22) | (1.01-1.30) | |||||||
Polynesian | 11.16 ± 1.54 | 10.23 ± 2.04 | 0.93 | 1.54 | 0.14 | 1.32 | 0.21 | 5.11 |
(-0.31, 2.18) | (0.85-2.05) | |||||||
European Caucasian | 3.02 ± 1.60 | 2.94 ± 1.52 | 0.08 | 0.75 | 0.45 | 1.01 | 0.80 | 0.04 |
(-0.13, 0.28) | (0.93-1.11) |