Identification of rheumatoid arthritis-associated PADI4, SLC22A4/A5, FCRL3 & PTPN22

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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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




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


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



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


susceptibleJIAcontrolRAcontrol

SNP No.allele(n=526)(n=259)(n=1033)(n=993)

C0.350.220.00020.230.200.013

pdcd1

Allele frequencySwedishJapanese



A0.0850.0730.05300

ptpn22

Allele frequencyWhite AmericanJapanese



T0.140.090.000700

tnfrsr1b

TNFRSF1B

Allele frequencyCaucasiansJapanese



T0.670.260.02060.870.170.0256

0.740.8311/22

TNFRSF1B




T0.670.740.02060.870.830.0256

tnfrsr1b

PADI4

PADI4




T0.450.420.310.460.370.00046

P --2

---------------------------------------------

P z

---------------------------------------------

1 0.3100000 1237 0.4958503

2 0.0004600 1478 3.3139134

---------------------------------------------



= 3.97074

= 1

P = 0.04630


N fs.05 = 3.36

========================================

Graph4

0.26

0.74

ctla4

EnglishJapanese



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

---------------------------------------------



= 0.62927

= 1

P = 0.42762


N fs.05 = 0.69

========================================

mif




C0.350.220.00020.230.200.013

pdcd1




A0.0850.0730.05300

ptpn22




T0.140.090.000700

tnfrsr1b

TNFRSF1B




T0.670.260.02060.870.170.0256

0.740.8311/22

TNFRSF1B




T0.670.740.02060.870.830.0256

tnfrsr1b

PADI4

PADI4




T0.450.420.310.460.370.00046

P --2

---------------------------------------------

P z

---------------------------------------------

1 0.3100000 1237 0.4958503

2 0.0004600 1478 3.3139134

---------------------------------------------



= 3.97074

= 1

P = 0.04630


N fs.05 = 3.36

========================================

MBD003A5BDA.xls

Graph16

0.62

0.38

Sheet1



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


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



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


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




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


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




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


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



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

---------------------------------------------



= 0.62927

= 1

P = 0.42762


N fs.05 = 0.69

========================================

mif




C0.350.220.00020.230.200.013

pdcd1




A0.0850.0730.05300

ptpn22




T0.140.090.000700

tnfrsr1b

TNFRSF1B




T0.670.260.02060.870.170.0256

0.740.8311/22

TNFRSF1B




T0.670.740.02060.870.830.0256

tnfrsr1b

PADI4

PADI4




T0.450.420.310.460.370.00046

P --2

---------------------------------------------

P z

---------------------------------------------

1 0.3100000 1237 0.4958503

2 0.0004600 1478 3.3139134

---------------------------------------------



= 3.97074

= 1

P = 0.04630


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

Identification of rheumatoid arthritis-associated PADI4, SLC22A4/A5, FCRL3 & PTPN22

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Transcript of Identification of rheumatoid arthritis-associated PADI4, SLC22A4/A5, FCRL3 & PTPN22