Only SNPs genotyped in this study are listed by name.

<p>SNPs in linkage disequilibrium with SNPs genotyped in this study are shown in brown. SNPs in gray were not genotyped or haplotype tagged due to low minor allele frequency (MAF). SNP - Single Nucleotide Polymorphism. 5251* is not yet registered in dbSNP as described in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000424#s2" target="_blank">methods</a>.</p

Odds ratios for the protective effect of the rs231778 G allele in African Americans with RA.

<p>Analysis compares number of patients and controls for genotype AA vs those with either AG or GG in a 2×2 Fisher's exact test. OR – odds ratio; CI – confidence interval.</p

Association with rheumatoid arthritis at rs231778 in African Americans.

<p>Values indicate number of samples with allele frequency in parentheses. Analysis compares number of patients and controls for each genotype (AA vs AG vs GG) in a 3×2 Fisher's exact test.</p

This plot, generated from HaploView v3.31 (Broad Institute), shows the r² values between SNPs genotyped in <i>CTLA4</i>.

<p>Darker boxes represent stronger r² values. 5251* is not yet registered in dbSNP as described in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000424#s2" target="_blank">methods</a>.</p

Mean percentage of European ancestry segregated by genotype of rs231778.

<p>This table provides data for the 347 samples with complete admixture and rs231778 genotyping data. Standard error is provided in parenthesis. Brackets indicate frequency counts used in determining association of the rs231778 G allele with rheumatoid arthritis among 366 samples, as described in the text.</p

Minor allele frequency (MAF) of rs231778 segregated by HLA-DRB1 shared epitope status.

<p>This table combines samples from both CLEAR I and CLEAR II and only incorporates data where HLA-DRB1 shared epitope (SE) status has been determined. The ‘N’ listed below each MAF represents the number of ‘G’ alleles over the total number of alleles for each number of SE alleles present. SE – <i>HLA-DRB1</i> shared epitope.</p

Minor allele frequencies of CTLA4 SNPs for African American RA patients and controls.

<p>This table represents combined data from CLEAR I and CLEAR II. rs3087243 (+60C/T) has been associated with RA in Caucasians, and rs231775 (+49A/G) has been associated with other autoimmune conditions. Position is the physical location of each polymorphism relative to the start codon (position = 0) in dbSNP build 129. CCP refers to anti-cyclic citrullinated antibody status. SE refers to presence of HLA-DRB1 shared epitope. Public databases include allele frequencies from HapMap or SeattleSNP. rs231776 was not in Hardy-Weinberg Equilibrium. *5251 is not currently listed in dbSNP as described in the <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1000424#s2" target="_blank">methods</a>.</p

IBD mapping of the pedigree with RA.

<p>(A) We investigated the novel non-parametric linkage analysis method which enabled the IBD mapping for the disease with any types of inheritance modes. Affected cases should carry one or two copy of the mutation which resides on a single ancestral haplotype in IBD, thus, SNPs adjacent to the causal mutation lose homozygous genotypes for at least one of the alleles. Our method searched the regional IBD stretches where SNP genotypes of the affected cases followed this rule, and then imputed presence or absence of the ancestral haplotype in the other unaffected subjects separately. (B) Results of the IBD mapping in the consanguineous pedigree with RA. Mapped IBD stretches are indicated as the bands colored in red. As the pedigree members used for the IBD mapping increased (left panel; 5 RA cases and 1 ACPA-positive unaffected subject, right panel; all available subjects), IBD stretches narrowed down (see detailed process in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087645#pone.0087645.s003" target="_blank">Table S2</a>). Candidate causal SNVs and Indels obtained after whole-genome exome sequencing were indicated as the triangles colored in blue and orange, respectively. The variants included and not included in the IBD stretches of each stages are indicated with filled and non-filled colors. Finally, only one SNV at 2p23 was included in the defined IBD stretch (right panel).</p

Results of rare variant tests for <i>PLB1</i> coding variants in the European RA case-control cohort.

a<p>Low-frequency rare coding variant (MAF≤0.01) obtained from deep sequencing of 1,088 RA cases and 1,088 controls were selected.</p><p>RA; rheumatoid arthritis, ACPA; anti-citrullinated protein antibodies.</p><p>BURDEN; burden test, VT; variable threshold test, FRQWGT; frequency-weighted test, CALPHA; C-alpha test, SKAT; sequence kernel association test.</p

Results of the validation assay for candidate variants derived from exome sequencing.

a<p>Genes of which variants were shared among 5 RA cases and 1 ACPA+ unaffected subject are indicated.</p>b<p>Based on NCBI Build 37/hg19.</p>c<p>Mid-P value of Fisher's exact test for RA cases and unaffected subjects are indicated.</p><p>RA; rheumatoid arthritis, ACPA; anti-citrullinated protein antibodies.</p