Background
Methods
Recruitment and ascertainment
African Americans (AAs) | European American (EAs) | |||
---|---|---|---|---|
SD cases (n = 1,562)
|
Contols (n = 343)
|
SD cases (n = 981)
|
Contols (n = 351)
| |
AD, n (%) | 1064 (68.1%) | 0 (0%) | 671 (68.4%) | 0 (0%) |
CD, n (%) | 1309 (83.8%) | 0 (0%) | 696 (70.9%) | 0 (0%) |
OD, n (%) | 358 (22.9%) | 0 (0%) | 577 (58.8%) | 0 (0%) |
MjD, n (%) | 531 (34.0%) | 0 (0%) | 318 (32.4%) | 0 (0%) |
AD + CD + OD + MjD, n(%) | 87 (5.6%) | 0 (0%) | 131 (13.4%) | 0 (0%) |
AD + CD + OD, n(%) | 196 (12.5%) | 0 (0%) | 283 (28.8%) | 0 (0%) |
AD + OD + MjD, n(%) | 90 (5.8%) | 0 (0%) | 141 (14.4%) | 0 (0%) |
AD + CD + MjD, n(%) | 360 (23.0%) | 0 (0%) | 195 (19.9%) | 0 (0%) |
CD + OD + MjD, n(%) | 116 (7.4%) | 0 (0%) | 182 (18.6%) | 0 (0%) |
AD + CD, n(%) | 854 (54.7%) | 0 (0%) | 476 (48.5%) | 0 (0%) |
AD + OD, n(%) | 217 (13.9%) | 0 (0%) | 321 (32.7%) | 0 (0%) |
AD + MjD, n(%) | 424 (27.1%) | 0 (0%) | 232 (23.6) | 0 (0%) |
CD + OD, n(%) | 303 (19.4%) | 0 (0%) | 436 (44.4%) | 0 (0%) |
CD + MjD, n(%) | 454 (29.1%) | 0 (0%) | 260 (26.5%) | 0 (0%) |
OD + MjD, n(%) | 123 (7.9%) | 0 (0%) | 206 (21.0%) | 0 (0%) |
Male, n (%) | 786 (50.5%) | 153 (44.6%) | 485 (49.4%) | 190 (54.1%) |
χ2 = 3.45, df = 1, P = 0.063 | χ2 = 1.70, df = 1, P = 0.192 | |||
Age, years | 39 ± 9 | 39 ± 9 | 38 ± 12 | 41 ± 13 |
t = −1.029, P = 0.304 (2-tailed) | t = 4.76, P = 2.2 × 10-6 (2-tailed) |
Genotyping
ID | SNPs | Chromosome | Gene | Allele | |||
---|---|---|---|---|---|---|---|
Position (hg18) | Location | MAF (AAs) | MAF (EAs) | ||||
RGS17_1 | rs9397578 | 153371201 |
RGS17
| 3' near gene | A/G | 0.27 (A) | 0.26 (A) |
RGS17_2 | rs7750874 | 153372161 |
RGS17
| 3' near gene | A/T | 0.29 (A) | 0.34 (A) |
RGS17_3 | rs503366 | 153375243 |
RGS17
| Intron 4 | C/T | 0.47 (C) | 0.49 (C) |
RGS17_4 | rs610614 | 153383477 |
RGS17
| Intron 4 | C/T | 0.42 (C) | 0.31 (C) |
RGS17_5 | rs545323 | 153387002 |
RGS17
| Intron 4 | C/T | 0.05 (C) | 0.33 (C) |
RGS17_6 | rs516557 | 153395551 |
RGS17
| Intron 2 | C/T | 0.47 (T) | 0.47 (C) |
RGS17_7 | rs9371276 | 153410854 |
RGS17
| Intron 1 | C/T | 0.48 (T) | 0.30 (C) |
RGS17_8 | rs1933258 | 153419500 |
RGS17
| Intron 1 | C/G | 0.49 (G) | 0.3 (C) |
RGS17_9 | rs9397585 | 153438568 |
RGS17
| Intron 1 | C/T | 0.49 (C) | 0.37 (C) |
RGS17_10 | rs685826 | 153452948 |
RGS17
| Intron 1 | C/T | 0.46 (T) | 0.44 (C) |
RGS17_11 | rs6931160 | 153472144 |
RGS17
| Intron 1 | C/G | 0.50 (G) | 0.44 (C) |
RGS17_12 | rs1281962 | 153473069 |
RGS17
| Intron 1 | C/G | 0.24 (G) | 0.46 (G) |
RGS17_13 | rs596359 | 153498746 |
RGS17
| 5' near gene | A/G | 0.33 (G) | 0.48 (G) |
RGS20_1 | rs1384797 | 54956481 |
RGS20
| intron 1 | A/G | 0.40 (G) | 0.02 (G) |
RGS20_2 | rs2220093 | 54963880 |
RGS20
| intron 1 | A/G | 0.36 (A) | 0.10 (G) |
RGS20_3 | rs1483537 | 54980301 |
RGS20
| intron 1 | A/G | 0.35 (G) | 0.01 (G) |
RGS20_4 | rs7824575 | 54984872 |
RGS20
| intron 1 | A/G | 0.24 (G) | 0.27 (A) |
RGS20_5 | rs2128821 | 55006166 |
RGS20
| intron 1 | C/G | 0.42 (C) | 0.26 (G) |
RGS20_6 | rs9298496 | 55018233 |
RGS20
| intron 2 | C/T | 0.37 (C) | 0.34 (C) |
RGS20_7 | rs6981243 | 55029044 |
RGS20
| intron 3 | A/C | 0.42 (A) | 0.41 (C) |
RGS20_8 | rs7009781 | 55035764 |
RGS20
| downstream | C/T | 0.27 (T) | 0.17 (C) |
Statistical analysis
Bioinformatics and genotype-expression analysis
Results
Allelic association
SNPs | Trait | Race | RA | Frequency | χ2 |
P
obs
| OR (95%CI) |
P
adj
| OR (95%CI) |
P
emp
|
---|---|---|---|---|---|---|---|---|---|---|
rs545323 | AD | AA | C | 0.06\0.03 | 6.70 | 0.010 | 1.96 (1.17−3.30) | 0.013 | 1.96 (1.16−3.32) | 0.010 |
CD | AA | C | 0.05\0.03 | 6.74 | 0.009 | 1.95 (1.17−3.25) | 0.015 | 1.95 (1.16−3.28) | 0.009 | |
OD | AA | C | 0.07\0.03 | 11.27 | 0.001 | 2.55 (1.45−4.49) | 0.002 | 2.51 (1.41−4.46) | 0.003 | |
MjD | AA | C | 0.06\0.03 | 7.30 | 0.007 | 2.10 (1.21−3.64) | 0.009 | 2.10 (1.20−3.67) | 0.009 | |
rs516557 | AD | AA | T | 0.49\0.43 | 4.78 | 0.029 | 1.25 (1.02−1.52) | 0.035 | 1.23 (1.02−1.50) | 0.018 |
rs9371276 | OD | EA | C | 0.33\0.27 | 7.47 | 0.006 | 1.34 (1.09−1.66) | 0.008 | 1.33 (1.08−1.63) | 0.008 |
MjD | EA | C | 0.33\0.27 | 5.11 | 0.024 | 1.32 (1.04−1.62) | 0.053 | 1.26 (1.00−1.58) | 0.032 | |
rs1933258 | CD | EA | C | 0.31\0.27 | 4.54 | 0.033 | 1.25 (1.02−1.54) | 0.04 | 1.25 (1.01−1.54) | 0.037 |
OD | EA | C | 0.33\0.27 | 8.51 | 0.004 | 1.37 (1.11−1.70) | 0.004 | 1.36 (1.10−1.68) | 0.005 | |
MjD | EA | C | 0.33\0.27 | 5.63 | 0.018 | 1.34 (1.05−1.70) | 0.036 | 1.29 (1.02−1.63) | 0.024 | |
rs9397585 | OD | EA | C | 0.40\0.35 | 4.39 | 0.036 | 1.24 (1.01−1.51) | 0.02 | 1.27 (1.04−1.56) | 0.028 |
MjD | EA | C | 0.41\0.35 | 4.36 | 0.037 | 1.27 (1.02−1.59) | 0.035 | 1.28(1.02−1.61) | 0.030 | |
rs6931160 | MjD | AA | G | 0.47\0.53 | 6.35 | 0.012 | 0.78 (0.64−0.95) | 0.015 | 0.79 (0.65−0.95) | 0.016 |
OD | EA | C | 0.48\0.42 | 5.14 | 0.023 | 1.25 (1.03−1.51) | 0.019 | 1.26 (1.04−1.54) | 0.018 | |
CD | AA | G | 0.49\0.53 | 4.56 | 0.033 | 0.83 (0.7−0.99) | 0.036 | 0.83 (0.70−0.99) | 0.028 | |
rs596359 | AD | AA | G | 0.35\0.29 | 7.82 | 0.005 | 1.31 (1.08−1.58) | 0.008 | 1.29 (1.07−1.56) | 0.005 |
AD | EA | G | 0.50\0.44 | 6.37 | 0.012 | 1.27 (1.05−1.52) | 0.011 | 1.27 (1.06−1.53) | 0.014 | |
CD | AA | G | 0.34\0.29 | 6.77 | 0.009 | 1.28 (1.06−1.54) | 0.011 | 1.27 (1.06−1.53) | 0.009 | |
CD | EA | G | 0.51\0.44 | 6.91 | 0.009 | 1.28 (1.06−1.54) | 0.008 | 1.29 (1.07−1.56) | 0.006 | |
OD | AA | G | 0.35\0.29 | 6.50 | 0.011 | 1.34 (1.07−1.69) | 0.023 | 1.31 (1.04−1.63) | 0.019 | |
OD | EA | G | 0.5\0.44 | 5.54 | 0.019 | 1.26 (1.04−1.52) | 0.01 | 1.29 (1.06−1.57) | 0.013 | |
MjD | AA | G | 0.35\0.29 | 8.05 | 0.005 | 1.35 (1.10−1.67) | 0.008 | 1.33 (1.08−1.63) | 0.006 | |
MjD | EA | G | 0.51\0.44 | 5.70 | 0.017 | 1.30 (1.05−1.62) | 0.015 | 1.31 (1.05−1.63) | 0.013 |
Haplotype association
LD Blocks | Haplotypes | Phenotypes | Frequencies | χ2 |
P
obs
|
P
emp
|
---|---|---|---|---|---|---|
(AAs)
|
(Case/control)
| |||||
RGS17_I | GATTC | AD | 0.053\ 0.032 | 5.09 | 0.024 | 0.319 |
GATTC | CD | 0.053\ 0.032 | 5.41 | 0.020 | 0.267 | |
GATTC | OD | 0.067\ 0.032 | 9.25 | 0.002 | 0.026 | |
GATTC | MjD | 0.057\ 0.032 | 5.95 | 0.015 | 0.178 | |
GTTCT | AD | 0.015\ 0.029 | 5.83 | 0.016 | 0.222 | |
GTTCT | CD | 0.016\ 0.029 | 5.44 | 0.020 | 0.265 | |
GTTCT | OD | 0.010\ 0.029 | 6.65 | 0.010 | 0.106 | |
GTTCT | MjD | 0.010\ 0.029 | 8.44 | 0.004 | 0.048 | |
RGS17_II | CCT | OD | 0.056\ 0.032 | 4.49 | 0.034 | 0.375 |
TGT | OD | 0.437\ 0.491 | 4.16 | 0.042 | 0.436 | |
TGT | MjD | 0.440\ 0.491 | 4.35 | 0.037 | 0.405 | |
RGS17_III | CC | MjD | 0.528\ 0.472 | 5.35 | 0.021 | 0.240 |
LD Blocks
|
Haplotypes
|
Phenotypes
|
Frequencies
|
χ
2
|
P
obs
|
P
emp
|
(EAs)
|
(Case/Control)
| |||||
RGS17_I | GTCTT | AD | 0.211\ 0.258 | 5.75 | 0.017 | 0.159 |
GTCTT | CD | 0.206\ 0.258 | 7.14 | 0.008 | 0.070 | |
GTCTT | OD | 0.210\ 0.258 | 5.56 | 0.018 | 0.169 | |
RGS17_II | CCCC | CD | 0.302\ 0.260 | 4.07 | 0.044 | 0.387 |
CCCC | OD | 0.324\ 0.260 | 8.26 | 0.004 | 0.028 | |
CCCC | MjD | 0.309\ 0.260 | 3.98 | 0.046 | 0.345 | |
RGS17_III | CC | OD | 0.471\ 0.420 | 4.56 | 0.033 | 0.317 |