Background
Methods
Characteristics of data
Gene Symbol | Locus | No. of SNPs |
---|---|---|
TNFRSF1B
| 1p36.22 | 20 |
PADI4
| 1p36.13 | 16 |
PTPN22
| 1p13.3 | 7 |
FCGR3A
| 1q23.3 | 1 |
IL1B
| 2q14 | 14 |
ITGAV
| 2q32.1 | 16 |
STAT4
| 2q32.3 | 35 |
CTLA4
| 2q33 | 16 |
IL3
| 5q31.1 | 3 |
IL13
| 5q31.1 | 3 |
IL4
| 5q31.1 | 4 |
SLC22A4
| 5q31.1 | 14 |
HAVCR1
| 5q33.3 | 13 |
NFKBIL1
| 6p21.3 | 7 |
HLA-DRB1
| 6p21.3 | 6 |
LTA
| 6p21.33 | 4 |
TNF
| 6p21.3 | 1 |
MAP3K7IP2
| 6q25.1 | 52 |
IL6
| 7p21 | 96 |
TRAF1
| 9q33 | 3 |
C5 | 9q33 | 27 |
DLG5
| 10q22.3 | 26 |
MS4A1
| 11q12.2 | 11 |
CARD15
| 16q12.1 | 10 |
RUNX1
| 21q22.12 | 216 |
MIF
| 22q11.23 | 18 |
Total | 639 |
Statistical model
Allelic score | ||||
---|---|---|---|---|
Genotype | AB | Ab | aB | ab |
(AA, BB) | 1 | 0 | 0 | 0 |
(AA, Bb) | 1/2 | 1/2 | 0 | 0 |
(AA, bb) | 0 | 1 | 0 | 0 |
(Aa, BB) | 1/2 | 0 | 1/2 | 0 |
(Aa, Bb) | 1/4 | 1/4 | 1/4 | 1/4 |
(Aa, bb) | 0 | 1/2 | 0 | 1/2 |
(aa, BB) | 0 | 0 | 1 | 0 |
(aa, Bb) | 0 | 0 | 1/2 | 1/2 |
(aa, bb) | 0 | 0 | 0 | 1 |
Score statistic by logistic regression model
Extension of Cochran-Armitage trend regression
Simulation study of power and type I error rates and comparison of genotype-based method
Allele-based method | Genotype-based method | |||||
---|---|---|---|---|---|---|
Type I error rate | Power | Power | ||||
Model | Score | F -test | Score | F -test | Score | MDR |
Dom ∪ Rec | 1.1 | 1.1 | 17.3 | 16.65 | 9.85 | 6.3 |
Modified | 0.78 | 0.84 | 23.95 | 23.45 | 13.75 | 9.3 |
Dom ∩ Dom | 0.8 | 0.84 | 46.75 | 46.15 | 29.3 | 24.5 |
Rec ∪ Rec | 1.22 | 1.26 | 58.2 | 57.7 | 38.1 | 31.9 |
Threshold | 1 | 1.04 | 92 | 91.75 | 80.45 | 73.45 |
Dom ∩ Rec | 0.92 | 0.94 | 96.45 | 96.3 | 88.95 | 82.6 |
Non-nested model comparison using Cochran-Armitage regression method
Analysis procedure
Step 1
Step 2
Step 3
Results
p-valueb | |||||||||
---|---|---|---|---|---|---|---|---|---|
Gene 1 symbol (location) | Gene 2 symbol (location) | SNP1a from gene 1 | SNP 2a from gene 2 | Function of SNP 1 | Function of SNP 2 | Score | F-test | Main vs. interaction | |
PADI4 (1p36.13) | X | TRAF1(9q33) | rs6586516, rs2477142 | rs3761847 | 5' UTR | 5' UTR | 1.66 × 10-8 | 1.43 × 10-8 | 0.005 |
PTPN22 (1p13.3) | X | SLC22A4(5q31.1) | rs2476601 | rs2306772 | Coding | intron | 1.79 × 10-12 | 1.25 × 10-12 | 0.0054 |
PTPN2 (1p13.3) | X | IL6 (7p21) | rs2476601 | rs2905325, rs1476482, rs2106549 | Coding | 5' UTR | 3.80 × 10-13 | 2.53 × 10-13 | 0.0003 |
SLC22A4 (5q31.1) | X | TRAF1 (9q33) | rs2073838, rs2306772 | rs881375 | Intron | 3' UTR | 6.19 × 10-9 | 5.22 × 10-9 | 0.0037 |
SLC22A4 (5q31.1) | X | C5 (9q33) | rs2073838, rs2306772 | rs2900180 | Intron | 3' UTR | 1.37 × 10-9 | 1.13 × 10-9 | 0.0029 |
NFKBIL1 (6p21.3) | X | HLA-DRB1(6p21.3) | rs4947324c | rs477515, rs2516049, rs532098 | 3' UTR | 5' UTR | <1.0 × 10-15 | <1.0 × 10-15 | 0.0012 |
HLA-DRB1 (6p21.3) | X | IL6 (7p21) | rs477515, rs2516049 | rs2961280, rs2961283, rs2905308 | 5' UTR | 5' UTR | <1.0 × 10-15 | <1.0 × 10-15 | 0.0023 |
HLA-DRB1 (6p21.3) | X | RUNX1(21q22.12) | rs660895 | rs2834779 | 5' UTR | 5' UTR | <1.0 × 10-15 | <1.0 × 10-15 | 0.0028 |
HLA-DRB1 (6p21.3) | X | RUNX1 (21q22.12) | rs660895, rs532098 | rs4817699, rs8131102, rs9984470, rs9979153 | 5' UTR | Intron | <1.0 × 10-15 | <1.0 × 10-15 | 0.0037 |
TRAF1 (9q33) | X | RUNX1 (21q22.12) | rs881375d | rs4816502, rs2242720e | 3' UTR | Intron/5' UTR | 3.03 × 10-8 | 2.62 × 10-8 | 0.0027 |
TRAF1 (9q33) | X | RUNX1 (21q22.12) | rs3761847 | rs1981392, rs2834714, rs4816502, rs2242882, rs932284 | 5' UTR | Intron | 1.29 × 10-11 | 9.47 × 10-12 | 0.0001 |
C5 (9q33) | X | RUNX1 (21q22.12) | rs10760130 | rs1981392, rs2834714, rs4816502, rs2242882 | 3' UTR | Intron | 7.19 × 10-11 | 5.53 × 10-11 | 0.0001 |
C5 (9q33) | X | RUNX1 (21q22.12) | rs2900180d | rs4816502, rs2242720e | 3' UTR | Intron/5' UTR | 2.83 × 10-10 | 2.24 × 10-10 | 0.0046 |
C5 (9q33) | X | RUNX1 (21q22.12) | rs1468673, rs10818500 | rs2834714, rs4816502 | Intron | Intron | 1.85 × 10-8 | 1.59 × 10-8 | 0.0001 |