Identification of rheumatoid arthritis-associated PADI4, SLC22A4/A5, FCRL3 & PTPN22International Symposium on Inflammatory Diseases of Barrier Organs3-4 June 2005, Kiel, GermanyRyo YamadaCenter for Genomic MedicineKyoto UniversityKyoto, Japan
Genetics and Genetic Analysis of Rheumatoid ArthritisTwin and family studiesRelative risk to monozygotic twin ( MZ )12~62Relative risk to siblings (sib)2~17HLA locus explains 1/3-1/2 of total genetic components.There are multiple non-HLA genes.Multiple linkage studiesMany candidate-approach studies
Major findings from SNP-based studiesPADI4 : RAPost-translational enzyme to produce targets of the most RA-specific autoantibodies.SLC22A4 /A5 : RA & CrohnErgothioneine or carnitine transporter expressed in hematologic lineages.PTPN22 : T1DM, SLE, RA & AITDLymphoid-specific intracellular phophataseFCRL3 : RA, SLR & AITDFc receptor homolog on B-cell membrane
Ca2+-dependent post-translational modificationLoss of ionic NH2+ of Arg residueEffects on intra- and inter- molecular interactions
K Arita M Sato et al. Nat Str & Mol Biol 2004Ca2+-dependent post-translational modification
PADI4CitrullinationAntigenicity
Human and Mouse PADI Gene cluster
Association Plots in the PADI Cluster-log10(P)PADI4
Enzyme substrate
Hypothetical mechanism of RA-susceptible variant
Following studiesCase-control association studiesUK (Barton, A. J., Worthington et al. 2004 Arthritis & Rheum): Similar allele frequencyNo statistical significanceJapanese (Kuwahara, M., Kamatani, N et al. 2004 ACR Poster)Allelic effect on expressionHigher concentration of PADI4 in PBMC from individuals with more copies of RA-susceptible haplotype(Harney, S.M., Brown, M.A. et al. 2004 ACR Poster)Allelic effect on autoantibody-productionCombinatorial effect on anti-CCP Ab production between HLA and PADI4 polymorphisms(Constantin, A., Cantagrel, A., et al. 2004 ACR Poster)
SLC22A4(/A5)Sugar transporter signaturesequence motifNC1234567891011Nucleotide binding motif****+++++
The SNPs associated with RA or Crohn diseaseRILSLC22A4SLC22A5IRF110kbGenesExonsSNPsRUNX1 binding siteRA & CrohnCrohnL503FHeat shock element-binding sitePsoriatic ArthritisTokuhiro, S. et al.Peltekova, V. D. et al.Barton, A. et al.JapaneseCaucasian
Ethnic difference in allele frequency of disease-related SNPsMori, et al. J Hum Genet 2005 May 10
JapaneseCaucasian0W01M00W01M0 0M1 1M1Assumption of common responsible variant Segregation
FCRL3Fc Receptor-like 3Transmembranous protein 734aa)FcR homolog Ig-like domains outsideMultiple tyrosin motifs (ITAM, ITIM, hemi-ITAM)Expressed by B cells in germinal centers
FCRL3 and others in 1q21-23FcRI
FCRL1~5CD1
FcRII/IIICD3Z1q21mCh3
1q23mCh1Psoriasis Multiple sclerosisRASLELupus models(sle1, swrl1)CIAMcia2)EAE,TMEVD(Eae3, Tmevd2)NOD(Idd10, Idd17)
NFkB regulates FCRL3 expressionBinds C > T
Lymphoid organs and B cell- specific expression
Expression of FCRL3 in lymphocyte aggregates in RA synovial tissueT-cellCD3100xB-cellCD20100xFCRL3Antisense100x400x
RAFCRL3(
PTPN221p13110kDa intracellular tyrosine phosphataseFunctional SNP 1858 C->T, R620W)Positive associationIDDM (Caucasian, Italian)Bottini N et al. RA (Caucasian)Begovich AB et al.SLE (Caucasian)Kyogoku, C. et al.No Tryptophan (W) allele in Japanese
J C A P value FST P value FST P value FST
SNP1 0.00 0.08 0.02
Connection of multiple autoimmune diseases by susceptible genes/loci
MAnti-oxydant transporter
PADI44SNPs SLC22A43SNPs Ergothioneine SLC22A51SNP carnitine PDCD1 1SNP PTPN22 1SNP TCRlocusgene SNPSLC22A4/A5Crohn SLE T1D1
2
3
4
SNP J C A PADI4
SLC22A4/5
SLC22A4/5
PDCD1 PTPN22 RAJC C RA J C Crohn
Crohn C (J:) RA, SLE C T1D
RA, SLE C T1D
CaucasianJapanesePDCD1MIF1CTLA4SLC22A4/A5PTPN22TNFRSF1PADI4Susceptible allelePreliminary calculation with random-effect model
Graph7
0.073
0.927
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph8
0
1
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph9
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph10
0
1
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph11
0.2160.216
0.7840.784
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph12
0.2160.216
0.7840.784
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph16
0.62
0.38
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph17
0.42
0.58
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph18
0.37
0.63
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph19
0.42
0.58
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph20
0
1
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph2
0.26
0.74
ctla4
EnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=123)(n=349)(n=781)(n=487)
G0.430.360.0280.650.620.215
0.215,1268
0.028,472
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.2150000 1268 0.7891917
2 0.0280000 472 1.9110356
---------------------------------------------
z(overall) = 1.90935
p(overall) = 0.02811
= 0.62927
= 1
P = 0.42762
effect size r = 0.0457731
N fs.05 = 0.69
========================================
mif
Allele frequencyEnglishJapanese
susceptibleJIAcontrolRAcontrol
SNP No.allele(n=526)(n=259)(n=1033)(n=993)
C0.350.220.00020.230.200.013
pdcd1
Allele frequencySwedishJapanese
casecontrolcasecontrol
SNP No.Allele(n=1175)(n=3404)(n=824)(n=649)
A0.0850.0730.05300
ptpn22
Allele frequencyWhite AmericanJapanese
casecontrolcasecontrol
SNP No.Allele(n=475)(n=475)(n=822)(n=649)
T0.140.090.000700
tnfrsr1b
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.260.02060.870.170.0256
0.740.8311/22
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.740.02060.870.830.0256
tnfrsr1b
PADI4
PADI4
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
T0.450.420.310.460.370.00046
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.3100000 1237 0.4958503
2 0.0004600 1478 3.3139134
---------------------------------------------
z(overall) = 2.69391
p(overall) = 0.00353
= 3.97074
= 1
P = 0.04630
effect size r = 0.0517009
N fs.05 = 3.36
========================================
Graph4
0.26
0.74
ctla4
EnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=123)(n=349)(n=781)(n=487)
G0.430.360.0280.650.620.215
0.215,1268
0.028,472
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.2150000 1268 0.7891917
2 0.0280000 472 1.9110356
---------------------------------------------
z(overall) = 1.90935
p(overall) = 0.02811
= 0.62927
= 1
P = 0.42762
effect size r = 0.0457731
N fs.05 = 0.69
========================================
mif
Allele frequencyEnglishJapanese
susceptibleJIAcontrolRAcontrol
SNP No.allele(n=526)(n=259)(n=1033)(n=993)
C0.350.220.00020.230.200.013
pdcd1
Allele frequencySwedishJapanese
casecontrolcasecontrol
SNP No.Allele(n=1175)(n=3404)(n=824)(n=649)
A0.0850.0730.05300
ptpn22
Allele frequencyWhite AmericanJapanese
casecontrolcasecontrol
SNP No.Allele(n=475)(n=475)(n=822)(n=649)
T0.140.090.000700
tnfrsr1b
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.260.02060.870.170.0256
0.740.8311/22
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.740.02060.870.830.0256
tnfrsr1b
PADI4
PADI4
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
T0.450.420.310.460.370.00046
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.3100000 1237 0.4958503
2 0.0004600 1478 3.3139134
---------------------------------------------
z(overall) = 2.69391
p(overall) = 0.00353
= 3.97074
= 1
P = 0.04630
effect size r = 0.0517009
N fs.05 = 3.36
========================================
MBD003A5BDA.xls
Graph16
0.62
0.38
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)P value(n=823)(n=655)P value
pdcd1_1A0.0850.0730.930.053001.00
ptpn22_1T0.140.090.910.0007001.00
mif_1C0.350.220.780.00020.230.200.800.013
tnfrsf1b_1T0.340.260.740.00590.870.870.130.7914
ctla4_1G0.430.360.640.0280.650.620.380.215
padi4_92T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
0
0
PDCD1 C
Sheet2
0
0
PDCD1 J
Sheet3
00000000
00000000
PTPN22 C
0
0
PTPN22 J
00
00
MIF11 C
00
00
MIF11 C
0
0
tnfrsf1b_1
0
0
TNFRSF1b_1
0
0
CTLA4 C
0
0
CTLA4 J
0
0
PADI4 C
0
0
PADI4 J
0
0
SLC22A4/A5
0
0
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)P value(n=823)(n=655)P value
pdcd1_1A0.0850.0730.930.053001.00
ptpn22_1T0.140.090.910.0007001.00
mif_1C0.350.220.780.00020.230.200.800.013
tnfrsf1b_1T0.340.260.740.00590.870.870.130.7914
ctla4_1G0.430.360.640.0280.650.620.380.215
padi4_92T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph15
0.36
0.64
Sheet1
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
Sheet1
PDCD1 C
Sheet2
PDCD1 J
Sheet3
PTPN22 C
PTPN22 J
MIF11 C
MIF11 C
tnfrsf1b_1
TNFRSF1b_1
CTLA4 C
CTLA4 J
PADI4 C
PADI4 J
SLC22A4/A5
SLC22A4/A5 J
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
A0.0850.0730.930.053001.00
T0.140.090.910.0007001.00
C0.350.220.780.00020.230.200.800.013
T0.340.260.740.00590.870.870.130.7914
G0.430.360.640.0280.650.620.380.215
T0.450.420.580.310.460.370.630.00046
SLC22A4/A5haplotype0.420.580.001.00
1-Pcont1-Pcont
0.073
0.927
0
1
0.090.090.090.090.090.090.090.09
0.910.910.910.910.910.910.910.91
0
1
0.2160.216
0.7840.784
0.2160.216
0.7840.784
0.26
0.74
0.87
0.13
0.36
0.64
0.62
0.38
0.42
0.58
0.37
0.63
0.42
0.58
0
1
Graph5
0.17
0.83
ctla4
EnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=123)(n=349)(n=781)(n=487)
G0.430.360.0280.650.620.215
0.215,1268
0.028,472
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.2150000 1268 0.7891917
2 0.0280000 472 1.9110356
---------------------------------------------
z(overall) = 1.90935
p(overall) = 0.02811
= 0.62927
= 1
P = 0.42762
effect size r = 0.0457731
N fs.05 = 0.69
========================================
mif
Allele frequencyEnglishJapanese
susceptibleJIAcontrolRAcontrol
SNP No.allele(n=526)(n=259)(n=1033)(n=993)
C0.350.220.00020.230.200.013
pdcd1
Allele frequencySwedishJapanese
casecontrolcasecontrol
SNP No.Allele(n=1175)(n=3404)(n=824)(n=649)
A0.0850.0730.05300
ptpn22
Allele frequencyWhite AmericanJapanese
casecontrolcasecontrol
SNP No.Allele(n=475)(n=475)(n=822)(n=649)
T0.140.090.000700
tnfrsr1b
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.260.02060.870.170.0256
0.740.8311/22
TNFRSF1B
Allele frequencyCaucasiansJapanese
casecontrolcasecontrol
SNP No.Allele(n=480)(n=137)(n=824)(n=648)
T0.670.740.02060.870.830.0256
tnfrsr1b
PADI4
PADI4
Allele frequencyEnglishJapanese
casecontrolcasecontrol
SNP No.Allele(n=772)(n=465)(n=823)(n=655)
T0.450.420.310.460.370.00046
P --2
---------------------------------------------
P z
---------------------------------------------
1 0.3100000 1237 0.4958503
2 0.0004600 1478 3.3139134
---------------------------------------------
z(overall) = 2.69391
p(overall) = 0.00353
= 3.97074
= 1
P = 0.04630
effect size r = 0.0517009
N fs.05 = 3.36
========================================
Lab. Rheumatic DiseasesDr. K. Yamamoto Dr. A. SuzukiDr. X. ChangDr. Y. KochiDr. S. TokuhiroMs. R. KawaidaMs. M. MoriMs. K. KobayashiMs. M. OhtakeMs. E. KannoMs. K. Komakine
SRC, RIKENDr. A. SekineDr. T. TsunodaDr. Y. NakamuraMr. H. KawakamiMr. T. KawaguchiClinical InstitutesDr. T. Sawada
And many other collaboratorsThank you all !
SLC22A4SLC22A4SNP
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