Association (conditional on linkage) results for 12 comparative pathogens.

<p>Focus is on the independent EBNA-1 associated SNPs rs477515/rs2516049 and rs2854275. There is no significant association of the top EBV SNPs with any of the other pathogens, after applying a Bonferroni correction to account for multiple testing (<i>p</i>≤0.05/12≈0.004).</p

<i>P</i>-values for EBNA-1 association, conditional on linkage, analysis for top systemic lupus erythematosus SNPs.

<p>Bold = <i>p</i>-value significant after Bonferoni correction for multiple testing (0.05/47≈1.06×10⁻³).</p

Genome-wide joint linkage and association analysis results for EBNA-1 antibody traits for SAFHS.

<p>(A) Quantitative antibody titer. (B) Discrete serostatus.</p

Association analysis given linkage.

<p>Shown are all SNPs yielding genome-wide significant <i>p</i>-values with either the quantitative and/or the qualitative antibody phenotype in the SAFHS. The regression coefficients refer to the estimated change in the phenotype for each dose of the rarer SNP allele. For the SAFHS all significant genome-wide results (<i>p</i>≤5.29×10⁻⁸) are presented in bold lettering. After correcting for multiple testing during replication in the SADGS (we tested the entire HLA region, with 5689 available SNPs: <i>p</i>≤0.05/5689≈8.79×10⁻⁶), there are two significant SNPs in the replication sample. When using the combined sample of both studies (SAFHS+SAFDGS), all SNPs originally significant in the SAFHS discovery sample are highly significant.</p>a<p>Since we used a liability threshold model for analysis of the dichotomous trait (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003147#s4" target="_blank">methods</a> section), the direction of effect on EBNA-1 discrete serostatus is opposite of the sign of the regression coefficient, but is in the same direction as the regression coefficient for the quantitative trait (e.g. for SNP rs204999, the minor allele is associated with a decrease in EBNA-1 antibody level and seronegativity).</p

<i>P</i>-values for EBNA-1 association, conditional on linkage, analysis for top Hodgkin lymphoma SNPs.

<p>Bold = <i>p</i>-value significant after Bonferoni correction for multiple testing (0.05/13≈3.85×10⁻³).</p

Heritability estimates of EBNA-1 quantitative antibody and discrete serostatus traits, with and without household effects.

a<p>Intermediate antibody titers were coded as unknown (indeterminate), thereby reducing the number of individuals included in analyses of the dichotomous serostatus trait.</p

EBV seroprevalence, based on measurement of anti-EBNA-1 antibodies, by sex and age for SAFHS.

<p>Sliding 15-year age windows are used to smooth the curves, and age shown is the midpoint of each age interval.</p

<i>P</i>-values for EBNA-1 association, conditional on linkage, analysis for top nasopharyngeal carcinoma SNPs.

<p>Bold = <i>p</i>-value significant after Bonferoni correction for multiple testing (0.05/23≈2.17×10⁻³).</p

Association analysis results (conditional on linkage) of extended HLA region for the combined sample (SAFHS+SAFDGS).

<p>The LD pattern was estimated based on SNP genotypes from study participants. SNPs in red are highly correlated with the top SNP associated with the EBNA-1 quantitative trait (rs477515/rs2516049). (A) Quantitative antibody titer. (B) Discrete serostatus.</p