Background
Methods
Study Population
Candidate genes and SNPs
Gene (Alias) | Marker | Chromosome | Chromosome position | RefSNP alleles | Call Rate (%) | MAF* (All subjects) | HWE P (controls) | MAF (White) | HWE** P (White controls) | MAF (Hispanic) | HWE P (Hispanic controls) |
---|---|---|---|---|---|---|---|---|---|---|---|
ALX1 (CART1)
| rs11608773 | 12 | 84229006 | A/G | 100.0 | 0.229 | 0.435 | 0.274 | 0.478 | 0.217 | 0.391 |
rs4761130 | 12 | 84226396 | C/T | 99.8 | 0.421 | 0.286 | 0.358 | 0.154 | 0.401 | 0.465 | |
rs7295242 | 12 | 84222948 | A/G | 100.0 | 0.161 | 0.781 | 0.074 | 0.557 | 0.159 | 0.358 | |
CARM1
| rs11667234 | 19 | 10880581 | A/C | 99.8 | 0.021 | 0.010 | 0.039 | 0.071 | 0.016 | 0.934 |
rs11670365 | 19 | 10865833 | C/T | 100.0 | 0.056 | 0.918 | 0.084 | 0.754 | 0.045 | 0.702 | |
rs1529711 | 19 | 10884434 | A/G | 99.7 | 0.097 | 0.492 | 0.161 | 0.932 | 0.081 | 0.519 | |
rs1541596 | 19 | 10848013 | A/G | 99.5 | 0.475 | 0.326 | 0.497 | 0.969 | 0.408 | 0.957 | |
rs17616105 | 19 | 10883159 | C/T | 100.0 | 0.189 | 0.732 | 0.235 | 0.365 | 0.152 | 0.072 | |
rs7254708 | 19 | 10863579 | A/G | 100.0 | 0.071 | 0.043 | 0.123 | 0.116 | 0.059 | 0.441 | |
CITED2
| rs1131431 | 6 | 139735527 | A/G | 100.0 | 0.153 | 0.273 | 0.200 | 0.624 | 0.121 | 0.948 |
rs7775752
| 6 | 139737486 |
A/G
|
45.1
|
0.007
|
0.957
|
0.009
|
0.913
|
0.006
|
1.000
| |
CREBBP (CBP)
| rs11076783 | 16 | 3722706 | C/T | 100.0 | 0.154 | 0.638 | 0.116 | 0.142 | 0.139 | 0.802 |
rs11076785
| 16 | 3730187 |
G/T
|
46.6
|
0.457
|
0.638
|
0.401
|
0.185
|
0.457
|
0.463
| |
rs11076786 | 16 | 3751597 | C/T | 100.0 |
0.075
|
0.008
| 0.077 | 0.441 | 0.046 | 0.637 | |
rs129986 | 16 | 3744242 | C/T | 100.0 | 0.023 | 0.530 | 0.032 | 0.590 | 0.020 | 0.735 | |
rs130003 | 16 | 3768173 | A/G | 99.8 | 0.015 | 0.792 | 0.032 | 0.711 | 0.010 | 0.967 | |
rs130008 | 16 | 3721953 | C/G | 99.8 | 0.011 | 0.838 | 0.032 | 0.752 | 0.001 | 1.000 | |
rs17136507 | 16 | 3740546 | C/T | 100.0 | 0.178 | 0.536 | 0.110 | 0.229 | 0.227 | 0.449 | |
rs886528 | 16 | 3751557 | C/T | 99.7 | 0.383 | 0.590 | 0.390 | 0.986 | 0.368 | 0.839 | |
rs9392 | 16 | 3715170 | A/G | 99.8 | 0.189 | 0.566 | 0.223 | 0.625 | 0.138 | 0.700 | |
EP300 (P300)
| rs17002284 | 22 | 39826792 | A/G | 100.0 | 0.265 | 0.220 | 0.313 | 0.745 | 0.217 | 0.522 |
rs17433014 | 22 | 39829768 | A/G | 99.8 | 0.018 | 0.769 | 0.029 | 0.793 | 0.019 | 0.834 | |
rs2230111 | 22 | 39851949 | A/G | 99.8 | 0.002 | 0.977 | 0.006 | 0.959 | 1.000 | 1.000 | |
rs4820428 | 22 | 39867535 | A/G | 100.0 |
0.446
|
0.006
| 0.329 | 0.822 | 0.419 | 0.667 | |
rs4820429 | 22 | 39868057 | C/G | 100.0 | 0.159 | 0.382 | 0.258 | 0.040 | 0.124 | 0.471 | |
rs4822006 | 22 | 39849308 | C/T | 100.0 | 0.247 | 0.844 | 0.355 | 0.587 | 0.185 | 0.740 | |
rs5758246 | 22 | 39871792 | A/G | 100.0 | 0.030 | 0.635 | 1.000 | 1.000 | 0.012 | 0.934 | |
rs9611502 | 22 | 39861182 | C/T | 100.0 | 0.014 | 0.838 | 0.019 | 0.918 | 0.013 | 0.867 | |
TFAP2A (AP2)
| rs10456013 | 6 | 10506548 | G/T | 100.0 | 0.032 | 0.592 | 0.048 | 0.670 | 0.026 | 0.735 |
rs1621700 | 6 | 10528084 | A/G | 99.7 | 0.288 | 0.671 | 0.252 | 0.081 | 0.357 | 0.773 | |
rs303050 | 6 | 10511169 | C/T | 100.0 | 0.257 | 0.061 | 0.165 | 0.259 | 0.262 | 0.267 | |
rs303055 | 6 | 10527462 | C/T | 100.0 | 0.353 | 0.150 | 0.435 | 0.569 | 0.335 | 0.025 | |
rs303056 | 6 | 10528467 | C/G | 100.0 | 0.159 | 0.229 | 0.094 | 0.477 | 0.126 | 1.000 | |
rs3798691 | 6 | 10519381 | C/G | 100.0 | 0.112 | 0.021 | 0.042 | 0.011 | 0.134 | 0.111 | |
rs3798694 | 6 | 10516743 | A/G | 100.0 | 0.062 | 0.122 | 0.087 | 0.225 | 0.059 | 0.293 | |
rs533558 | 6 | 10503558 | A/G | 100.0 | 0.441 | 0.848 | 0.361 | 0.955 | 0.481 | 0.858 | |
rs537112 | 6 | 10503192 | A/G | 100.0 | 0.180 | 0.571 | 0.103 | 0.754 | 0.195 | 0.255 |
Genotyping Approach
Analytic procedures
Results and Discussion
Variable | Spina Bifida | |
---|---|---|
Cases n = 297 (%1) | Controls n = 300 (%1) | |
Maternal Race/Ethnicity | ||
White, non-Hispanic | 59 (19.9) | 96 (32.0) |
Hispanic, Native Born | 33 (11.1) | 33 (11.0) |
Hispanic, Foreign Born | 166 (55.9) | 115 (38.3) |
Black | 17 (5.7) | 20 (6.7) |
Asian | 9 (3.0) | 25 (8.3) |
Other | 9 (3.0) | 11 (3.7) |
Maternal age at delivery (years) | ||
13-24 | 128 (43.1) | 123 (41.0) |
25-29 | 80 (26.9) | 71 (23.7) |
30-34 | 47 (15.8) | 64 (21.3) |
35-55 | 39 (13.1) | 42 (14.0) |
Maternal education | ||
Less than high school | 158 (53.2) | 110 (36.7) |
High School | 65 (21.9) | 81 (27.0) |
Greater than High school | 71 (23.9) | 109 (36.3) |
Parity | ||
0 | 120 (40.4) | 114 (38.0) |
1 | 88 (29.6) | 101 (33.7) |
≥ 2 | 86 (29.0) | 84 (28.0) |
Plurality | ||
Singleton | 287 (96.6) | 293 (97.7) |
Multiple births | 8 (2.7) | 7 (2.3) |
Infant Sex | ||
Male | 146 (49.2) | 149 (49.7) |
Female | 151 (50.8) | 151 (50.3) |
SNP | Gene | Ethnicity | refSNP alleles | Minor Allele | Ratio Counts (Case, Control) | P value | Odds Ratio | 95% CI |
---|---|---|---|---|---|---|---|---|
rs129986 |
CREBBP (CBP)
| white | C/T | T | 118:0, 182:10 | 0.008* | n/a | n/a |
rs17616105 |
CARM1
| white | C/T | C | 101:17, 136:56 | 0.003 | 2.45 | 1.34-4.46 |
rs303056 |
TFAP2A (AP2)
| white | C/G | C | 16:102, 13:179 | 0.046 | 2.16 | 1.00-2.15 |
rs3798691 |
TFAP2A (AP2)
| Hispanic | C/G | C | 65:333, 29:267 | 0.013 | 1.80 | 1.13-2.87 |
Hispanic-FB | C/G | C | 52:280, 22:208 | 0.036 | 1.76 | 1.03-2.98 | ||
rs533558 |
TFAP2A (AP2)
| Hispanic-NB | A/G | G | 36:30, 24:42 | 0.036 | 2.10 | 1.05-4.22 |
rs4820428 |
EP300 (P300)
| All subjects | A/G | G | 276:240, 229:259 | 0.038 | 1.30 | 1.01-1.67 |
Marker | Gene | Ethnicity |
P value | Mode of Inheritance | Odds Ratio [(ratio count (case, control)) | 95% CI |
---|---|---|---|---|---|---|
rs17002284 |
EP300
| All subjects | 0.012 | Recessive |
0.43 (13, 29; 284, 271)
|
0.22 - 0.84
|
rs4820428 |
EP300
| All subjects | 0.011 | Additive [(Dd) vs (dd)] |
1.46 (132, 122; 87, 117)
|
1.00 - 2.11
|
[(DD) vs (Dd)] | 1.18 (78, 61; 132, 122) | 0.78 - 1.79 | ||||
All subjects | 0.012 | Dominant |
1.54 (210, 183; 87, 117)
|
1.10 - 2.17
| ||
rs4820429 |
EP300
| All subjects | 0.046 | Dominant |
0.70 (75, 98; 222, 202)
|
0.49 - 0.99
|
White | 0.041 | Dominant |
0.50 (22, 52; 37, 44)
|
0.26 - 0.50
| ||
rs1621700 |
TFAP2A
| All subjects | 0.041 | Additive [(Dd) vs (dd)] | 1.30 (131, 118; 138, 161) | 0.92 - 1.81 |
[(DD) vs (Dd)] | 1.33 (28, 19; 131, 118) | 0.70 - 2.50 | ||||
rs3798691 |
TFAP2A
| Hispanic | 0.015 | Additive [(Dd) vs (dd)] |
1.78 (48, 23; 143, 122)
|
1.04 - 3.19
|
[(DD) vs (Dd)] | 1.40 (9, 3; 47, 22) | 0.35 - 5.70 | ||||
Hispanic | 0.022 | Dominant |
1.84 (56, 26; 143, 122)
|
1.13 - 3.25
| ||
Hispanic-FB | 0.049 | Dominant |
1.82 (44, 19; 122, 92)
|
1.00 - 3.40
| ||
rs533558 |
TFAP2A
| Hispanic-NB | 0.038 | Additive [(Dd) vs (dd)] | 3.00 (18, 14; 6, 14) | 0.92 - 9.80 |
[(DD) vs (Dd)] | 1.40 (9, 5; 18, 14) | 0.38 - 5.12 | ||||
Hispanic-NB | 0.032 | Dominant |
3.32 (27, 19; 6, 14)
|
1.08 - 10.18
| ||
rs17616105 |
CARM1
| Hispanic | 0.0 | Recessive | n/a (6, 0; 193, 148) | n/a |
White | 0.004 | Additive [(Dd) vs (dd)] | 0.48 (15, 36; 43,50) | 0.23 - 1.00 | ||
[(DD) vs (Dd)] | 0.24 (1,10; 15,36) | 0.03 - 2.04 | ||||
White | 0.010 | Dominant |
0.40 (16, 46; 43, 50)
|
0.40 - 0.20
| ||
rs1131431 |
CITED2
| White | 0.027 | Recessive |
5.32 (6, 2; 53, 94)
|
1.04 - 27.30
|
rs129986 |
CREBBP
| All subjects | 0.005 | Additive [(Dd) vs (dd)] |
0.27 (6, 21; 291, 279)
|
0.11 - 0.69
|
[(DD) vs (Dd)] | n/a (0, 0; 6, 21) | n/a | ||||
All subjects | 0.003 | Dominant |
0.27 (6, 21; 291, 279)
|
0.11 - 0.69
| ||
White | 0.014 | Additive [(Dd) vs (dd)] | n/a (0, 10; 59, 86) | n/a | ||
[(DD) vs (Dd)] | n/a (0, 0; 0, 10) | n/a | ||||
White | 0.010 | Dominant | n/a (0, 10; 59, 86) | n/a |
CITED2
EP300
Haplotype Block | Frequency | P Value | Odds Ratio (case, control) | 95% CI |
---|---|---|---|---|
TFAP2A-rs537112, rs533558, rs303050, rs3798694, and rs3798691 in Hispanic | ||||
AGCGC
|
0.133
|
0.0205
|
1.73 (63.0 : 335.0, 29.0 : 267.0)
|
1.08-2.77
|
GATGG | 0.516 | 0.2019 | 0.82 (197.0 : 201.0, 161.0 : 135.0) | 0.61-1.11 |
GGTGG | 0.201 | 0.8135 | 0.96 (78.9 : 319.1, 60.8 : 235.2) | 0.66-1.39 |
GGCAG | 0.058 | 0.4974 | 1.26 (25.0 : 373.0, 15.0 : 281.0) | 0.65-2.43 |
AGCGG | 0.041 | 0.3207 | 0.69 (13.9 : 384.1, 14.8 : 281.2) | 0.33-1.45 |
GGCGG | 0.028 | 0.6568 | 0.81 (10.1 : 387.9, 9.2 : 286.8) | 0.33-2.00 |
AGTGG | 0.021 | 0.9639 | 0.97 (8.1 : 389.9, 6.2 : 289.8) | 0.34-2.79 |
EP300- rs17002284, rs4822006, rs4820428 and rs4820429 in non-Hispanic white | ||||
ACGG
|
0.503
|
0.0377
|
1.30 (276.0 : 240.0, 229.0 : 259.0)
|
1.01-1.67
|
GCAG | 0.245 | 0.1665 | 0.82 (117.0 : 399.0, 129.0 : 359.0) | 0.61-1.09 |
ATAC | 0.163 | 0.054 | 0.72 (73.0 : 443.0, 91.0 : 397.0) | 0.51-1.00 |
ATAG | 0.072 | 0.8074 | 1.06 (38.0 : 478.0, 34.0 : 454.0) | 0.66-1.72 |
ACAG | 0.015 | 0.2348 | 1.91 (10.0 : 506.0, 5.0 : 483.0) | 0.65-5.63 |