Table 2.
8-SNP haplotype association tests for the best haplotype pattern (rs7550106, rs499697, rs17659389, rs17670505) derived by multi-locus stepwise regression (MSR) with four known FLG mutations (S3247X, R2447X, 2282del4, R501X) added in that order for case control set and replicated by family set.
| Case control set | Family set | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Freq. (n = 1914) | FLG (n = 1914) | NON-FLG (n = 1605) | FLG (268 families) | NON-FLG (162 families) | ||||||||||
| Haplotypes | Cases | Controls | OR | p value | OR | p value | Freq. | T:U | OR | p value | T:U | OR | p value | |
| 2222 | 2222 | 0.3656 | 0.4028 | 0.83 | 1.05 E-02 | 1.07 | 4.10E-01 | 0.3992 | 206.3:256.1 | 0.81 | 2.08 E-02 | 138.6:152.4 | 0.91 | 4.18 E-01 |
| 2222 | 2212 | 0.0102 | 0.0035 | 4.92 | 2.67 E-03 | 0.0039 | 2.0:6.0 | 0.33 | 1.58 E-01 | |||||
| 2222 | 2221 | 0.0052 | 0.0062 | 0.80 | 6.50 E-01 | 0.0011 | 2.1:0.1 | 38.89 | 1.66 E-01 | |||||
| 2222 | 2122 | 0.0030 | 0.0041 | 0.63 | 4.80 E-01 | NA | NA | NA | NA | |||||
| 2222 | Total | 0.3841 | 0.4166 | 0.85 | 2.43 E-02 | 0.4042 | 210.4:262.1 | 0.80 | 1.74 E-02 | |||||
| 2212 | 2222 | 0.1180 | 0.1392 | 0.78 | 2.43 E-02 | 0.95 | 6.34E-01 | 0.1077 | 110.6:91.8 | 1.20 | 1.86 E-01 | 66.5:59.6 | 1.11 | 5.42 E-01 |
| 2212 | 2212 | 0.0014 | 0.0018 | 0.53 | 6.35 E-01 | NA | NA | NA | NA | |||||
| 2212 | 2221 | 0.0010 | 0.0012 | 0.63 | 7.79 E-01 | 0.0011 | 1.1:1.1 | 1.00 | 1.00 E+00 | |||||
| 2212 | Total | 0.1204 | 0.1422 | 0.76 | 1.28 E-02 | 0.1088 | 111.7:92.9 | 1.20 | 1.89 E-01 | |||||
| 2122 | 2222 | 0.1289 | 0.1488 | 0.81 | 4.78 E-02 | 0.90 | 3.44E-01 | 0.1205 | 93.7:126.6 | 0.74 | 2.66 E-02 | 64.1:79.9 | 0.80 | 1.87 E-01 |
| 2122 | 2221 | 0.0241 | 0.0032 | 12.65 | 1.75 E-10 | 0.0267 | 35.2:18.3 | 1.92 | 2.07 E-02 | |||||
| 2122 | 2212 | 0.0123 | 0.0037 | 7.00 | 1.21 E-04 | 0.0068 | 7.0:8.0 | 0.87 | 7.91 E-01 | |||||
| 2122 | 2122 | 0.0114 | 0.0012 | 22.62 | 7.16 E-07 | 0.0115 | 15.0:9.0 | 1.67 | 2.21 E-01 | |||||
| 2122 | 2211 | 0.0034 | 0.0000 | NA | NA | NA | NA | NA | NA | |||||
| 2122 | Total | 0.1800 | 0.1569 | 1.23 | 2.69 E-02 | 0.1655 | 150.9:161.9 | 0.93 | 5.34 E-01 | |||||
| 2121 | 2212 | 0.0448 | 0.0028 | 31.26 | 3.10 E-24 | 0.0538 | 74.0:38.0 | 1.95 | 6.61 E-04 | |||||
| 2121 | 2222 | 0.0267 | 0.0295 | 0.88 | 5.63 E-01 | 0.97 | 8.94E-01 | 0.0123 | 11.8:13.8 | 0.85 | 6.92 E-01 | 5.7:9.7 | 0.59 | 3.08 E-01 |
| 2121 | 2221 | 0.0075 | 0.0000 | NA | NA | 0.0019 | 2.0:2.0 | 1.00 | 1.00 E+00 | |||||
| 2121 | Total | 0.0790 | 0.0322 | 2.65 | 5.22 E-10 | 0.0680 | 87.7:53.7 | 1.63 | 4.22 E-03 | |||||
| 2112 | 2222 | 0.0562 | 0.0892 | 0.49 | 2.43 E-06 | 0.59 | 8.22E-04 | 0.0582 | 46.8:68.0 | 0.69 | 4.73 E-02 | 24.2:36.3 | 0.67 | 1.19 E-01 |
| 2112 | 2212 | 0.0041 | 0.0016 | 6.23 | 4.20 E-02 | 0.0048 | 4.0:6.0 | 0.67 | 5.27 E-01 | |||||
| 2112 | 2221 | 0.0015 | 0.0010 | 2.59 | 4.73 E-01 | 0.0029 | 2.1:3.0 | 0.69 | 6.75 E-01 | |||||
| 2112 | Total | 0.0618 | 0.0917 | 0.60 | 3.89 E-04 | 0.0659 | 52.8:77.1 | 0.69 | 3.37 E-02 | |||||
| 1222 | 2222 | 0.0982 | 0.0785 | 1.36 | 1.69 E-02 | 1.71 | 5.55E-05 | 0.1186 | 124.8:88.6 | 1.41 | 1.30 E-02 | 92.0:54.9 | 1.68 | 2.19 E-03 |
| 1222 | 1222 | 0.0061 | 0.0010 | 8.05 | 2.77 E-03 | NA | NA | NA | NA | |||||
| 1222 | Total | 0.1043 | 0.0795 | 1.42 | 4.81 E-03 | 0.1186 | 124.8:88.6 | 1.41 | 1.30 E-02 | |||||
Logistic regression was used for testing a single haplotype for the case control set and the weighted TDT statistic was used for a single haplotype by computing transmitted (T) versus non-transmitted (U) haplotypes. Calculations were carried out for the full set (FLG) and the FLG reduced sets (NON-FLG). The minor allele was coded as 1 and the major one as 2. For the sake of following the rare FLG mutations the frequency threshold for the 8-SNP haplotype estimation had been lowered to 0.001, however, only combined with best pattern haplotypes down to a total frequency > 0.05 in the full case set.
Abbreviations are as follows: Freq., haplotype frequency; OR, odds ratio; FLG, Filaggrin gene; T:U, transmitted:non-transmitted; NA, not available.