TABLE E1. List of Snps in a Total of 26 Loci Identified Through GWAS of Atopic Dermatitis

TABLE E1. List of SNPs in a total of 26 loci identified through GWAS of atopic dermatitis and eosinophilic esophagitis

Gene / Location / SNP (reported) / SNP (tested) / References
Atopic dermatitis
FLG / 1q21 / rs6661961 / rs6696556* / E1
C11orf30/LRRC32 / 11q13.5 / rs7927894 / rs11236809* / E1
TMEM232/SLC25A46 / 5q22.1 / rs7701890 / rs9326801* / E2
TNFRSF6B/ZGPAT / 20q13.33 / rs6010620 / rs6010620* / E2
OVOL1 / 11q13.1 / rs479844 / rs593982* / E3
ACTL9 / 19p13.2 / rs2164983 / rs4804075* / E3
KIF3A/IL13† / 5q31.1 / rs2897442 / rs1295686* / E3
IL1RL1/IL18R1/IL18RAP / 2q12 / rs13015714 / rs13015714 / E4
GLB1 / 3p21.33 / rs6780220 / rs6780220 / E4
CCDC80 / 3q13.2 / rs12634229 / rs12634229 / E4
GPSM3 (MHC region) / 6p21.3 / rs176095 / rs176095 / E4
CARD11 / 7p22 / rs4722404 / rs4722404 / E4
ZNF365 / 10q21.2 / rs10995251 / rs10995251 / E4
OR10A3/NLRP10 / 11p15.4 / rs878860 / rs878860 / E4
CYP24A1/PFDN4 / 20q13 / rs16999165 / rs16999165 / E4
IL2/IL21 / 4q27 / rs17389644 / rs17389644 / E5
PRR5L / 11p13 / rs12295535 / rs12295535 / E5
CLEC16A/DEXI / 16p13.13 / rs2041733 / rs2041733 / E5
ZNF652 / 17q21.32 / rs16948048 / rs16948048 / E5
Eosinophilic esophagitis
TSLP/WDR36 / 5q22 / rs3806932 / rs3806932 / E6
CAPN14 / 2p23 / rs77569859 / rs77569859 / E7
XKR6 / 8p23 / rs2898261 / rs2898261 / E7
LOC283710/KLF13 / 15q13 / rs8041227 / rs8041227 / E7
C11orf30 / 11q13.5 / rs55646091 / rs55646091 / E8
STAT6 / 12q13.3 / rs167769 / rs167769 / E8
ANKRD27 / 19q13.11 / rs3815700 / rs3815700 / E8

*SNPs that had the top signals in our previous GWAS (ref. E4) for the reported loci.

†The reported locus at5q31.1 was KIF3A in the original GWAS (ref. E3). However, the most significant association at the locuswas observed at rs1295686 in the IL13gene in our previous GWAS (ref. E4).

TABLE E2. Basic characteristics of study population

Primary set / Validation set
Case
Total number of samples / 593 / 279
Age (mean ± s.d.) / 5.2±3.7 / 5.8±3.3
Male/Female (Male %) / 419/174 (70.7) / 188/91 (67.4)
Atopic dermatitis (%) / 376 (63.4) / 190 (68.1)
Bronchial asthma (%) / 220 (37.1) / 113 (40.5)
Anaphylaxis (%) / 268 (45.2) / 145 (52.0)
Anaphylactic shock (%) / 48 (8.1) / 35 (12.5)
Total IgEkU/L (mean ± s.e.m.) / 642.5±98.9 / 623.5±91.2
Allergens
Egg (%) / 369 (62.2) / 205 (73.5)
Milk (%) / 254 (42.8) / 149 (53.4)
Wheat (%) / 128 (21.6) / 111 (39.8)
Peanut (%) / 93 (15.7) / 18 (6.5)
Control
Total number of samples / 985 / 886
Age (mean ± s.d.) / 50.0±9.2 / 50.6±12.9
Male/Female (Male %) / 449/536 (45.6) / 590/296 (66.6)

TABLE E3.Detailed results of theprimary and validation studies

Gene
SNP ID / Allele / RAF
Chr / Risk / Stage / Cases / Controls / P*† / OR (95%CI) / Phet‡
Atopic dermatitis
FLG / T/G / Primary / 0.885 / 0.880 / .68 / 1.05(0.84-1.31)
rs6696556 / G / Validation / 0.884 / 0.869 / .37 / 1.15(0.86-1.54)
1q21 / Combined / 0.885 / 0.875 / .39 / 1.08(0.91-1.30) / .628
C11orf30/LRRC32 / T/G / Primary / 0.280 / 0.224 / .00056 / 1.34(1.14-1.59)
rs11236809 / G / Validation / 0.312 / 0.255 / .0096 / 1.33(1.08-1.63)
11q13.5 / Combined / 0.290 / 0.239 / .000014 / 1.34(1.17-1.52) / .914
TMEM232/SLC25A46 / A/C / Primary / 0.186 / 0.147 / .0037 / 1.33(1.09-1.61)
rs9326801 / A / Validation / 0.160 / 0.163 / .87 / 0.98(0.75-1.27)
5q22.1 / Combined / 0.178 / 0.155 / .031 / 1.19(1.01-1.39) / .065
TNFRSF6B/ZGPAT / A/G / Primary / 0.336 / 0.314 / .19 / 1.11(0.95-1.29)
rs6010620 / G / Validation / 0.355 / 0.316 / .082 / 1.19(0.98-1.46)
20q13.33 / Combined / 0.342 / 0.315 / .039 / 1.14(1.01-1.29) / .572
OVOL1 / T/C / Primary / 0.569 / 0.518 / .0049 / 1.23(1.06-1.42)
rs593982 / C / Validation / 0.566 / 0.558 / .72 / 1.04(0.86-1.26)
11q13.1 / Combined / 0.568 / 0.537 / .016 / 1.15(1.03-1.30) / .167
ACTL9 / A/G / Primary / 0.175 / 0.170 / .68 / 1.04(0.86-1.26)
rs4804075 / A / Validation / 0.172 / 0.173 / .97 / 1.00(0.77-1.28)
19p13.2 / Combined / 0.174 / 0.171 / .79 / 1.02(0.88-1.19) / .785
KIF3A/IL13 / T/C / Primary / 0.372 / 0.291 / .0000031 / 1.44(1.23-1.68)
rs1295686 / T / Validation / 0.364 / 0.299 / .0038 / 1.34(1.10-1.64)
5q31.1 / Combined / 0.369 / 0.295 / .000000067 / 1.40(1.24-1.59) / .584
IL1RL1/IL18R1/IL18RAP / T/G / Primary / 0.426 / 0.425 / .95 / 1.00(0.87-1.16)
rs13015714 / G / Validation / 0.437 / 0.418 / .44 / 1.08(0.89-1.31)
2q12 / Combined / 0.429 / 0.421 / .61 / 1.03(0.92-1.16) / .551
GLB1 / A/C / Primary / 0.591 / 0.508 / .0000082 / 1.40(1.21-1.62)
rs6780220 / C / Validation / 0.575 / 0.531 / .064 / 1.20(0.99-1.45)
3p21.33 / Combined / 0.586 / 0.519 / .0000025 / 1.32(1.17-1.49) / .203
CCDC80 / T/C / Primary / 0.364 / 0.313 / .0039 / 1.26(1.08-1.46)
rs12634229 / C / Validation / 0.373 / 0.323 / .030 / 1.24(1.02-1.52)
3q13.2 / Combined / 0.367 / 0.318 / .00028 / 1.25(1.11-1.41) / .937
GPSM3 (MHC region) / A/G / Primary / 0.825 / 0.827 / .91 / 0.99(0.82-1.20)
rs176095 / A / Validation / 0.821 / 0.813 / .68 / 1.05(0.82-1.35)
6p21.3 / Combined / 0.824 / 0.820 / .91 / 1.01(0.87-1.18) / .697
CARD11 / T/C / Primary / 0.338 / 0.333 / .77 / 1.02(0.88-1.19)
rs4722404 / C / Validation / 0.344 / 0.335 / .68 / 1.04(0.85-1.27)
7p22 / Combined / 0.340 / 0.334 / .64 / 1.03(0.91-1.17) / .886
ZNF365 / T/C / Primary / 0.580 / 0.511 / .00017 / 1.32(1.14-1.53)
rs10995251 / C / Validation / 0.530 / 0.497 / .18 / 1.15(0.95-1.39)
10q21.2 / Combined / 0.564 / 0.504 / .00013 / 1.25(1.11-1.41) / .242
OR10A3/NLRP10 / T/C / Primary / 0.556 / 0.534 / .21 / 1.10(0.95-1.27)
rs878860 / C / Validation / 0.599 / 0.536 / .010 / 1.29(1.07-1.57)
11p15.4 / Combined / 0.570 / 0.535 / .010 / 1.16(1.03-1.31) / .182
CYP24A1/PFDN4 / T/C / Primary / 0.721 / 0.701 / .24 / 1.10(0.94-1.29)
rs16999165 / T / Validation / 0.707 / 0.701 / .80 / 1.03(0.83-1.27)
20q13 / Combined / 0.717 / 0.701 / .27 / 1.07(0.94-1.22) / .600
IL2/IL21 / A/G / Primary / 0.113 / 0.101 / .28 / 1.14(0.90-1.44)
rs17389644 / A / Validation / 0.149 / 0.105 / .0049 / 1.49(1.13-1.97)
4q27 / Combined / 0.124 / 0.103 / .0096 / 1.27(1.06-1.52) / .146
PRR5L / T/C / Primary / 0.030 / 0.019 / - / 1.63(1.03-2.60)
rs12295535 / T / Validation / 0.032 / 0.033 / - / 0.98(0.57-1.68)
11p13 / Combined / 0.031 / 0.025 / .14 / 1.30(0.91-1.86) / .157
CLEC16A/DEXI / A/G / Primary / 0.708 / 0.677 / .074 / 1.15(0.99-1.35)
rs2041733 / A / Validation / 0.707 / 0.672 / .12 / 1.18(0.96-1.45)
16p13.13 / Combined / 0.707 / 0.675 / .019 / 1.16(1.02-1.32) / .886
ZNF652 / A/G / Primary / 0.150 / 0.129 / .093 / 1.20(0.97-1.47)
rs16948048 / G / Validation / 0.174 / 0.130 / .0096 / 1.41(1.08-1.82)
17q21.32 / Combined / 0.158 / 0.129 / .0039 / 1.27(1.08-1.50) / .346
Eosinophilic esophagitis
TSLP/WDR36 / A/G / Primary / 0.307 / 0.271 / .032 / 1.19(1.02-1.40)
rs3806932 / G / Validation / 0.308 / 0.279 / .19 / 1.15(0.94-1.42)
5q22 / Combined / 0.307 / 0.275 / .012 / 1.18(1.03-1.34) / .801
CAPN14 / A/G / Primary / 0.958 / 0.952 / .43 / 1.15(0.81-1.63)
rs77569859 / A / Validation / 0.968 / 0.954 / .16 / 1.46(0.87-2.45)
2p23 / Combined / 0.961 / 0.953 / .16 / 1.24(0.93-1.68) / .462
XKR6 / T/G / Primary / 0.922 / 0.924 / .88 / 0.98(0.75-1.28)
rs2898261 / G / Validation / 0.928 / 0.918 / .40 / 1.16(0.81-1.67)
8p23 / Combined / 0.924 / 0.921 / .74 / 1.04(0.84-1.30) / .459
LOC283710/KLF13 / A/G / Primary / 0.019 / 0.020 / - / 0.95(0.57-1.60)
rs8041227 / A / Validation / 0.027 / 0.012 / - / 2.21(1.14-4.30)
15q13 / Combined / 0.022 / 0.017 / .23 / 1.29(0.83-1.98) / .047
C11orf30 / A/G / Primary / 0.000 / 0.000 / - / -
rs55646091 / - / Validation / 0.000 / 0.000 / - / -
11q13.5 / Combined / 0.000 / 0.000 / - / -
STAT6 / T/C / Primary / 0.237 / 0.198 / .0082 / 1.26(1.06-1.50)
rs167769 / T / Validation / 0.237 / 0.199 / .060 / 1.24(0.99-1.56)
12q13.3 / Combined / 0.237 / 0.199 / .0014 / 1.25(1.09-1.44) / .926
ANKRD27 / A/G / Primary / 0.303 / 0.293 / .55 / 1.05(0.90-1.23)
rs3815700 / G / Validation / 0.319 / 0.326 / .76 / 0.97(0.79-1.19)
19q13.11 / Combined / 0.308 / 0.309 / .80 / 1.02(0.90-1.15) / .545

RAF: risk allele frequency, OR: odds ratio, CI: confidence interval.*P values of the Cochran-Armitage trend test for each stage. †Results of combined analyses were calculated by the Mantel-Haenszel method. ‡Results from the Breslow-Day test.

TABLE E4. Detailed results of the primary and validation studies of the sex-adjusted analysis

Gene
SNP ID / Allele / Raw / Sex-adjusted
Chr / Risk / Stage / P*† / OR (95%CI) / P*† / OR (95%CI)
Atopic dermatitis
FLG / T/G / Primary / .68 / 1.05(0.83-1.32) / .78 / 1.03(0.82-1.30)
rs6696556 / G / Validation / .37 / 1.14(0.90-1.43) / .37 / 1.14(0.90-1.43)
1q21 / Combined / .38 / 1.08(0.91-1.29) / .44 / 1.07(0.90-1.28)
C11orf30/LRRC32 / T/G / Primary / .00058 / 1.33(1.12-1.58) / .00060 / 1.34(1.13-1.59)
rs11236809 / G / Validation / .0099 / 1.31(1.11-1.55) / .0096 / 1.31(1.11-1.55)
11q13.5 / Combined / .000018 / 1.32(1.16-1.50) / .000018 / 1.33(1.17-1.51)
TMEM232/SLC25A46 / A/C / Primary / .0039 / 1.33(1.09-1.63) / .0052 / 1.33(1.09-1.63)
rs9326801 / A / Validation / .87 / 0.98(0.80-1.20) / .87 / 0.98(0.80-1.20)
5q22.1 / Combined / .027 / 1.19(1.02-1.40) / .034 / 1.19(1.01-1.39)
TNFRSF6B/ZGPAT / A/G / Primary / .19 / 1.11(0.95-1.30) / .19 / 1.11(0.95-1.30)
rs6010620 / G / Validation / .083 / 1.20(1.02-1.40) / .085 / 1.20(1.02-1.40)
20q13.33 / Combined / .037 / 1.14(1.01-1.29) / .036 / 1.14(1.01-1.29)
OVOL1 / T/C / Primary / .0050 / 1.24(1.06-1.44) / .0021 / 1.27(1.09-1.48)
rs593982 / C / Validation / .72 / 1.04(0.89-1.21) / .72 / 1.04(0.89-1.21)
11q13.1 / Combined / .014 / 1.16(1.03-1.30) / .0084 / 1.17(1.04-1.32)
ACTL9 / A/G / Primary / .68 / 1.04(0.85-1.27) / .38 / 1.09(0.90-1.33)
rs4804075 / A / Validation / .97 / 1.00(0.82-1.21) / .97 / 1.00(0.82-1.21)
19p13.2 / Combined / .76 / 1.02(0.88-1.19) / .51 / 1.05(0.90-1.23)
KIF3A/IL13 / T/C / Primary / .0000035 / 1.45(1.23-1.70) / .000014 / 1.43(1.22-1.68)
rs1295686 / T / Validation / .0039 / 1.35(1.15-1.58) / .0039 / 1.35(1.15-1.58)
5q31.1 / Combined / .000000056 / 1.41(1.25-1.60) / .00000021 / 1.40(1.23-1.58)
IL1RL1/IL18R1/IL18RAP / T/G / Primary / .95 / 1.00(0.87-1.16) / .76 / 1.02(0.88-1.19)
rs13015714 / G / Validation / .44 / 1.08(0.93-1.25) / .43 / 1.08(0.93-1.25)
2q12 / Combined / .60 / 1.03(0.92-1.16) / .47 / 1.04(0.93-1.17)
GLB1 / A/C / Primary / .0000090 / 1.39(1.20-1.61) / .0000083 / 1.40(1.21-1.63)
rs6780220 / C / Validation / .065 / 1.20(1.04-1.39) / .064 / 1.20(1.04-1.39)
3p21.33 / Combined / .0000031 / 1.32(1.17-1.48) / .0000032 / 1.33(1.18-1.49)
CCDC80 / T/C / Primary / .0040 / 1.24(1.07-1.45) / .0029 / 1.26(1.08-1.48)
rs12634229 / C / Validation / .031 / 1.25(1.07-1.46) / .031 / 1.25(1.07-1.46)
3q13.2 / Combined / .00032 / 1.25(1.11-1.40) / .00024 / 1.26(1.11-1.42)
GPSM3 (MHC region) / A/G / Primary / .91 / 0.99(0.82-1.20) / .79 / 0.97(0.81-1.18)
rs176095 / A / Validation / .68 / 1.05(0.87-1.28) / .68 / 1.05(0.87-1.27)
6p21.3 / Combined / .88 / 1.01(0.87-1.17) / .97 / 1.00(0.86-1.17)
CARD11 / T/C / Primary / .77 / 1.02(0.88-1.19) / .87 / 1.01(0.87-1.18)
rs4722404 / C / Validation / .68 / 1.04(0.89-1.22) / .67 / 1.04(0.90-1.22)
7p22 / Combined / .63 / 1.03(0.91-1.16) / .70 / 1.02(0.91-1.16)
ZNF365 / T/C / Primary / .00018 / 1.32(1.14-1.54) / .00014 / 1.34(1.15-1.56)
rs10995251 / C / Validation / .18 / 1.14(0.98-1.32) / .18 / 1.14(0.98-1.32)
10q21.2 / Combined / .00016 / 1.25(1.11-1.40) / .00015 / 1.25(1.12-1.41)
OR10A3/NLRP10 / T/C / Primary / .21 / 1.10(0.94-1.27) / .19 / 1.11(0.95-1.28)
rs878860 / C / Validation / .010 / 1.29(1.11-1.49) / .010 / 1.29(1.11-1.49)
11p15.4 / Combined / .011 / 1.16(1.03-1.30) / .0088 / 1.17(1.04-1.32)
CYP24A1/PFDN4 / T/C / Primary / .24 / 1.10(0.93-1.29) / .33 / 1.08(0.92-1.28)
rs16999165 / T / Validation / .80 / 1.03(0.87-1.21) / .80 / 1.03(0.87-1.21)
20q13 / Combined / .27 / 1.07(0.95-1.22) / .35 / 1.06(0.93-1.21)
IL2/IL21 / A/G / Primary / .28 / 1.13(0.90-1.43) / .27 / 1.14(0.90-1.44)
rs17389644 / A / Validation / .0052 / 1.49(1.18-1.88) / .0053 / 1.49(1.18-1.88)
4q27 / Combined / .0094 / 1.26(1.06-1.51) / .0083 / 1.27(1.06-1.52)
PRR5L / T/C / Primary / .036 / 1.66(1.02-2.70) / .021 / 1.78(1.09-2.89)
rs12295535 / T / Validation / .94 / 0.98(0.60-1.60) / .94 / 0.98(0.60-1.59)
11p13 / Combined / .12 / 1.32(0.93-1.89) / .095 / 1.36(0.95-1.96)
CLEC16A/DEXI / A/G / Primary / .074 / 1.15(0.98-1.36) / .15 / 1.13(0.96-1.33)
rs2041733 / A / Validation / .13 / 1.18(1.00-1.39) / .12 / 1.18(1.00-1.39)
16p13.13 / Combined / .019 / 1.16(1.03-1.32) / .036 / 1.15(1.01-1.30)
ZNF652 / A/G / Primary / .094 / 1.19(0.97-1.47) / .18 / 1.16(0.94-1.42)
rs16948048 / G / Validation / .0099 / 1.41(1.14-1.74) / .0098 / 1.41(1.14-1.74)
17q21.32 / Combined / .0037 / 1.27(1.08-1.49) / .0076 / 1.25(1.06-1.47)
Eosinophilic esophagitis
TSLP/WDR36 / A/G / Primary / .032 / 1.19(1.01-1.40) / .021 / 1.21(1.03-1.43)
rs3806932 / G / Validation / .19 / 1.15(0.97-1.35) / .19 / 1.15(0.97-1.35)
5q22 / Combined / .013 / 1.17(1.03-1.33) / .0089 / 1.19(1.04-1.35)
CAPN14 / A/G / Primary / .43 / 1.15(0.80-1.65) / .26 / 1.23(0.86-1.76)
rs77569859 / A / Validation / .16 / 1.45(1.01-2.07) / .16 / 1.45(1.01-2.07)
2p23 / Combined / .15 / 1.24(0.93-1.66) / .086 / 1.29(0.96-1.74)
XKR6 / T/G / Primary / .88 / 0.98(0.74-1.29) / .94 / 1.01(0.77-1.33)
rs2898261 / G / Validation / .40 / 1.17(0.89-1.54) / .41 / 1.17(0.89-1.54)
8p23 / Combined / .71 / 1.04(0.84-1.30) / .58 / 1.07(0.85-1.33)
LOC283710/KLF13 / A/G / Primary / .86 / 0.95(0.56-1.63) / .56 / 0.85(0.50-1.46)
rs8041227 / A / Validation / .018 / 2.25(1.31-3.85) / .018 / 2.25(1.31-3.85)
15q13 / Combined / .19 / 1.32(0.87-1.99) / .31 / 1.24(0.82-1.89)
C11orf30 / A/G / Primary / - / - / - / -
rs55646091 / - / Validation / - / - / - / -
11q13.5 / Combined / - / - / - / -
STAT6 / T/C / Primary / .0084 / 1.27(1.06-1.52) / .020 / 1.24(1.04-1.49)
rs167769 / T / Validation / .061 / 1.24(1.04-1.49) / .062 / 1.24(1.04-1.49)
12q13.3 / Combined / .0012 / 1.26(1.09-1.45) / .0028 / 1.24(1.08-1.43)
ANKRD27 / A/G / Primary / .55 / 1.05(0.89-1.23) / .42 / 1.07(0.91-1.26)
rs3815700 / G / Validation / .76 / 0.97(0.82-1.14) / .77 / 0.97(0.82-1.14)
19q13.11 / Combined / .78 / 1.02(0.90-1.15) / .67 / 1.03(0.91-1.17)

OR: odds ratio, CI: confidence interval. *P value of the logistic regression for each stage. †Results of combined analyses were calculated under the fixed effects model.

TABLE E5.Susceptibility loci recently identified by GWAS for allergy and related phenotypes

A total of 14 loci significantly associated with FA in this study
C11orf30/LRRC32 / 11q13.5 / Asthma / E14
AR / E15
AD / E1, E5, E16
IgE to grass / E15
Allergic sensitization / E17
TMEM232/SLC25A46 / 5q22.1 / AD / E2
IgE to grass / E15
Allergic sensitization / E17
TNFRSF6B/ZGPAT / 20q13.33 / AD / E3, E5
OVOL1 / 11q13.1 / AD / E3
KIF3A/IL13 / 5q31.1 / Asthma / E18, E19
AD / E3, E5, E16
Total IgE / E20, E21, E22
GLB1 / 3p21.33 / AD / E4
CCDC80 / 3q13.2 / AD / E4
ZNF365 / 10q21.2 / AD / E4
OR10A3/NLRP10 / 11p15.4 / AD / E4
IL2/IL21 / 4q27 / AD / E5
Allergic sensitization / E17, E23
CLEC16A/DEXI / 16p13.13 / AD / E5
ZNF652 / 17q21.32 / AD / E5
TSLP/WDR36 / 5q22 / EoE / E6
Asthma / E24
IgE to grass / E15
Allergic sensitization / E17
STAT6 / 12q13.3 / EoE / E8
Total IgE / E20, E21, E22
Allergic sensitization / E17
A total of 12 loci not associated with FA in this study
FLG / 1q21 / AD / E1, E3, E5, E16
ACTL9 / 19p13.2 / AD / E3
IL1RL1/IL18R1/IL18RAP / 2q12 / AD / E5
Asthma / E18, E23, E24, E25, E26, E27
Allergic sensitization / E17, E23
Blood eosinophil count / E25
GPSM3 (MHC region) / 6p21.3 / AD / E4, E16
Asthma / E24, E27, E28
Total IgE / E21, E22
IgE to grass / E15
Allergic sensitization / E17, E23
CARD11 / 7p22 / AD / E4
CYP24A1/PFDN4 / 20q13 / AD / E4
PRR5L / 11p13 / AD / E5
CAPN14 / 2p23 / EoE / E7
XKR6 / 8p23 / EoE / E7
LOC283710/KLF13 / 15q13 / EoE / E7
C11orf30 / 11q13.5 / EoE / E8
ANKRD27 / 19q13.11 / EoE / E8

Susceptibility loci recently identified by genome-wide association were reviewed in ref.5.

TABLE E6.Association analysis of childhood FA for FLG null variants

c.3321delA / p.Q1701* / p.S2554* / p.S2889* / p.S3296* / p.K4022* / Total(%††)
Primary set
Cases / AA† / 581 / 585 / 570 / 554 / 585 / 575 / 509
Aa† / 11 / 3 / 16 / 37 / 7 / 12 / 82
aa† / 0 / 0 / 0 / 0 / 0 / 0 / 2**
Total / 592 / 588 / 586 / 591 / 592 / 587 / 593 (14.2)
Controls / AA† / 965 / 975 / 961 / 956 / 979 / 950 / 886
Aa† / 18 / 3 / 18 / 27 / 3 / 30 / 95
aa† / 0 / 0 / 1 / 0 / 0 / 1 / 4**
Total / 983 / 978 / 980 / 983 / 982 / 981 / 985 (10.1)
P‡ / 1.00 / .68 / .39 / .0010 / .048 / .21 / .024
OR / 1.01 / 1.66 / 1.34 / 2.32 / 3.89 / 0.62 / 1.42
95%CI / 0.43-2.28 / 0.22-12.45 / 0.65-2.74 / 1.37-3.98 / 0.89-23.33 / 0.29-1.25 / 1.04-1.92
Validation set
Cases / AA† / 270 / 276 / 275 / 257 / 275 / 264 / 233
Aa† / 7 / 1 / 4 / 20 / 2 / 12 / 44
aa† / 0 / 0 / 0 / 0 / 0 / 1 / 2**
Total / 277 / 277 / 279 / 277 / 277 / 277 / 279 (16.5)
Controls / AA† / 873 / 875 / 878 / 854 / 873 / 864 / 810
Aa† / 11 / 1 / 6 / 27 / 11 / 20 / 74
aa† / 0 / 0 / 0 / 0 / 0 / 1 / 2**
Total / 884 / 876 / 884 / 881 / 884 / 885 / 886 (8.6)
P‡ / .16 / .42 / .26 / .0049 / .74 / .046 / .00035
OR / 2.04 / 3.16 / 2.12 / 2.41 / 0.58 / 2.06 / 2.04
95%CI / 0.67-5.80 / 0.04-248.19 / 0.44-8.98 / 1.27-4.49 / 0.06-2.66 / 0.97-4.24 / 1.38-3.01
Combined (Primary and Validation sets)
Pcombined§ / .43 / .45 / .21 / .000015 / .36 / .81 / .000055
OR / 1.31 / 1.95 / 1.47 / 2.36 / 1.53 / 1.06 / 1.63
95%CI / 0.68-2.47 / 0.36-10.66 / 0.77-2.77 / 1.58-3.52 / 0.58-3.85 / 0.63-1.74 / 1.28-2.07

OR: odds ratio, CI: confidence interval. †A: wild type, a: mutant type. ‡P value of the Fisher’s extract test for each stage. §Results of combined analyses were calculated by the Mantel-Haenszel method.**Three cases and three controls carried two different FLG mutations in the same individual, andweconfirmed themto be carrying compound heterozygous mutations by allele-specific cloning and sequencing. ††Percentage of subjects carryingone or more of the tested FLG mutations.

TABLE E7.Association results of FA with atopic dermatitis for 26SNPs

Gene / FA with atopic dermatitis
SNP ID / Allele / RAF / RAF
Chr / Risk / Stage / Controls / Cases / P*† / OR (95%CI) / Phet‡
Atopic dermatitis
FLG / T/G / Primary / 0.880 / 0.879 / .91 / 0.99(0.76-1.28)
rs6696556 / G / Validation / 0.869 / 0.892 / .23 / 1.25(0.88-1.78)
1q21 / Combined / 0.875 / 0.883 / .53 / 1.08(0.87-1.33) / .284
C11orf30/LRRC32 / T/G / Primary / 0.224 / 0.293 / .00025 / 1.43(1.18-1.73)
rs11236809 / G / Validation / 0.255 / 0.313 / .022 / 1.33(1.05-1.70)
11q13.5 / Combined / 0.239 / 0.300 / .000017 / 1.39(1.20-1.62) / .651
TMEM232/SLC25A46 / A/C / Primary / 0.147 / 0.181 / .026 / 1.28(1.03-1.60)
rs9326801 / A / Validation / 0.163 / 0.166 / .90 / 1.02(0.76-1.37)
5q22.1 / Combined / 0.155 / 0.176 / .076 / 1.18(0.98-1.41) / .228
TNFRSF6B/ZGPAT / A/G / Primary / 0.314 / 0.336 / .25 / 1.11(0.93-1.33)
rs6010620 / G / Validation / 0.316 / 0.358 / .10 / 1.21(0.96-1.52)
20q13.33 / Combined / 0.315 / 0.344 / .062 / 1.14(0.99-1.32) / .570
OVOL1 / T/C / Primary / 0.518 / 0.584 / .0018 / 1.30(1.10-1.54)
rs593982 / C / Validation / 0.558 / 0.571 / .63 / 1.06(0.84-1.32)
11q13.1 / Combined / 0.537 / 0.580 / .0067 / 1.21(1.05-1.39) / .142
ACTL9 / A/G / Primary / 0.830 / 0.832 / .89 / 1.02(0.81-1.27)
rs4804075 / G / Validation / 0.827 / 0.826 / .96 / 0.99(0.74-1.33)
19p13.2 / Combined / 0.829 / 0.830 / .96 / 1.01(0.84-1.21) / .905
KIF3A/IL13 / T/C / Primary / 0.291 / 0.399 / .000000081 / 1.61(1.35-1.92)
rs1295686 / T / Validation / 0.299 / 0.376 / .0029 / 1.41(1.12-1.78)
5q31.1 / Combined / 0.295 / 0.391 / .0000000024 / 1.54(1.33-1.77) / .376
IL1RL1/IL18R1/IL18RAP / T/G / Primary / 0.425 / 0.422 / .89 / 0.99(0.83-1.17)
rs13015714 / G / Validation / 0.418 / 0.432 / .64 / 1.06(0.84-1.32)
2q12 / Combined / 0.421 / 0.425 / .86 / 1.01(0.88-1.16) / .639
GLB1 / A/C / Primary / 0.508 / 0.598 / .000034 / 1.44(1.22-1.71)
rs6780220 / C / Validation / 0.531 / 0.568 / .18 / 1.16(0.93-1.45)
3p21.33 / Combined / 0.519 / 0.588 / .000034 / 1.33(1.16-1.53) / .134
CCDC80 / T/C / Primary / 0.313 / 0.376 / .0021 / 1.32(1.11-1.58)
rs12634229 / C / Validation / 0.323 / 0.395 / .0072 / 1.36(1.09-1.72)
3q13.2 / Combined / 0.318 / 0.383 / .000048 / 1.34(1.16-1.54) / .833
GPSM3 (MHC region) / A/G / Primary / 0.827 / 0.828 / .93 / 1.01(0.81-1.26)
rs176095 / A / Validation / 0.813 / 0.832 / .39 / 1.13(0.85-1.52)
6p21.3 / Combined / 0.820 / 0.830 / .59 / 1.05(0.88-1.27) / .537
CARD11 / T/C / Primary / 0.667 / 0.681 / .50 / 1.06(0.89-1.27)
rs4722404 / T / Validation / 0.665 / 0.655 / .70 / 0.96(0.76-1.21)
7p22 / Combined / 0.666 / 0.672 / .77 / 1.02(0.89-1.18) / .476
ZNF365 / T/C / Primary / 0.511 / 0.592 / .00014 / 1.39(1.17-1.65)
rs10995251 / C / Validation / 0.497 / 0.534 / .20 / 1.16(0.93-1.45)
10q21.2 / Combined / 0.504 / 0.573 / .00013 / 1.30(1.14-1.49) / .208
OR10A3/NLRP10 / T/C / Primary / 0.534 / 0.576 / .051 / 1.19(1.00-1.41)
rs878860 / C / Validation / 0.536 / 0.603 / .019 / 1.31(1.05-1.65)
11p15.4 / Combined / 0.535 / 0.585 / .0028 / 1.23(1.07-1.41) / .476
CYP24A1/PFDN4 / T/C / Primary / 0.299 / 0.284 / .46 / 0.93(0.77-1.12)
rs16999165 / C / Validation / 0.299 / 0.329 / .24 / 1.15(0.91-1.46)
20q13 / Combined / 0.299 / 0.299 / .91 / 1.01(0.87-1.17) / .170
IL2/IL21 / A/G / Primary / 0.101 / 0.105 / .72 / 1.05(0.80-1.39)
rs17389644 / A / Validation / 0.105 / 0.150 / .013 / 1.50(1.09-2.07)
4q27 / Combined / 0.103 / 0.120 / .067 / 1.22(0.98-1.51) / .097
PRR5L / T/C / Primary / 0.019 / 0.029 / - / 1.57(0.92-2.68)
rs12295535 / T / Validation / 0.033 / 0.026 / - / 0.79(0.40-1.57)
11p13 / Combined / 0.025 / 0.028 / .45 / 1.18(0.76-1.79) / .120
CLEC16A/DEXI / A/G / Primary / 0.677 / 0.719 / .035 / 1.22(1.01-1.47)
rs2041733 / A / Validation / 0.672 / 0.746 / .0048 / 1.44(1.11-1.85)
16p13.13 / Combined / 0.675 / 0.728 / .00076 / 1.29(1.11-1.51) / .311
ZNF652 / A/G / Primary / 0.129 / 0.154 / .087 / 1.23(0.97-1.57)
rs16948048 / G / Validation / 0.130 / 0.176 / .017 / 1.43(1.06-1.93)
17q21.32 / Combined / 0.129 / 0.162 / .0054 / 1.31(1.08-1.58) / .452
Eosinophilic esophagitis
TSLP/WDR36 / A/G / Primary / 0.271 / 0.299 / .16 / 1.15(0.95-1.38)
rs3806932 / G / Validation / 0.279 / 0.297 / .48 / 1.09(0.86-1.40)
5q22 / Combined / 0.275 / 0.298 / .12 / 1.13(0.97-1.31) / .765
CAPN14 / A/G / Primary / 0.952 / 0.961 / .28 / 1.26(0.83-1.93)
rs77569859 / A / Validation / 0.954 / 0.971 / .14 / 1.63(0.86-3.08)
2p23 / Combined / 0.953 / 0.965 / .083 / 1.37(0.96-2.00) / .516
XKR6 / T/G / Primary / 0.076 / 0.086 / .38 / 1.15(0.85-1.56)
rs2898261 / T / Validation / 0.082 / 0.074 / .56 / 0.89(0.58-1.35)
8p23 / Combined / 0.079 / 0.082 / .71 / 1.05(0.81-1.34) / .327
LOC283710/KLF13 / A/G / Primary / 0.020 / 0.020 / - / 0.98(0.54-1.79)
rs8041227 / A / Validation / 0.012 / 0.027 / - / 2.17(1.02-4.63)
15q13 / Combined / 0.017 / 0.022 / .31 / 1.29(0.77-2.11) / .102
C11orf30 / A/G / Primary / 0.000 / 0.000 / - / -
rs55646091 / - / Validation / 0.000 / 0.000 / - / -
11q13.5 / Combined / 0.000 / 0.000 / - / -
STAT6 / T/C / Primary / 0.198 / 0.229 / .075 / 1.20(0.98-1.47)
rs167769 / T / Validation / 0.199 / 0.224 / .29 / 1.16(0.88-1.51)
12q13.3 / Combined / 0.199 / 0.227 / .042 / 1.18(1.00-1.40) / .825
ANKRD27 / A/G / Primary / 0.293 / 0.303 / .59 / 1.05(0.87-1.26)
rs3815700 / G / Validation / 0.326 / 0.324 / .93 / 0.99(0.78-1.25)
19q13.11 / Combined / 0.309 / 0.310 / .71 / 1.03(0.89-1.19) / .693

RAF: risk allele frequency, OR: odds ratio, CI: confidence interval. *P value of the Cochran-Armitage trend test for each stage. †Results of combined analyses were calculated by the Mantel-Haenszel method. ‡Results from the Breslow-Day test.