Schematic representation of the included methods.

<p>GV indicates genetic variant; MV, multivariate; PCHAT, Principal Component of Heritability Association Test; T1, trait 1; T2, trait 2; T3, trait 3; TATES, Trait-based Association Test that uses Extended Simes procedure; UV-MA, meta-analysis of univariate results; UV-PCA, univariate analysis of first principal component.</p

Power of the methods for scenarios with one of three traits associated with the QTL (A), two of three traits associated with the QTL (B) and with all three traits associated with the QTL (C).

<p>The explained variance of the QTL was fixed at 0.1%. For clarity reasons, we have not provided errors bars. Confidence ranges for the power estimates are all between 1 and 5%; exact values are provided in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095923#pone.0095923.s003" target="_blank">Tables S3</a>–<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0095923#pone.0095923.s005" target="_blank">S5</a>. MAF, minor allele frequency; MV, multivariate; PCHAT, Principal Component of Heritability Association Test; QTL, quantitative trait locus; rE, residual correlation; rG, genetic correlation induced by the QTL; TATES, Trait-based Association Test that uses Extended Simes procedure; UV-MA, meta-analysis of univariate results; UV-PCA, univariate analysis of first principal component; UV T1, univariate analysis of trait 1; UV T2, univariate analysis of trait 2; UV T3, univariate analysis of trait 3.</p

Simulation scenarios.

<p>MAF indicates minor allele frequency; j, trait; QTL, quantitative trait locus; rE, residual correlation; rG, genetic correlation.</p

SNP genotyping results in SAPHIR (n = 1,726) and NBS (n = 1,832).

<p> <u>Notes:</u></p><p>The coding of genotypes is indicated in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035015#pone-0035015-t002" target="_blank">Table 2</a>. SAPHIR data are indicated on the left side of the slash, and NBS data are given on the right side of the slash.</p><p>MAF… minor allele frequency.</p><p>CR… call rate (genotyping success rate).</p><p>HWE… p-value for test for Hardy-Weinberg-Equilibrium.</p

SNP genotypes of the family within the two genes <i>SLC11A2</i> and <i>TMPRSS6</i>.

<p>SNP genotypes of the family within the two genes <i>SLC11A2</i> and <i>TMPRSS6</i>.</p

Genetic association between iron and ferritin levels and SNPs in <i>SLC11A2</i> and <i>TMPRSS6</i> in SAPHIR.

<p><u>Note</u>: For linear regression, an additive genetic effect of the SNPs on the outcome variable was assumed; linear regression analyses were adjusted for age and gender. The p-values were based on the log-transformed model, and the β-estimates were based on the model on the original scale.</p

Laboratory parameters of the family at the time of taking of the first blood samples, and after intravenous iron administrations in the family's children suffering from IRIDA, i.e. Son 2, and Daughters 1 and 2.

<p><u>Notes</u>:</p>a<p>If reference values are different for males (m) and females (f), both reference values are indicated.</p>b<p>Reference values can be found at <a href="http://www.hepcidinanalysis.com" target="_blank">www.hepcidinanalysis.com</a> (date of consulting the website: January 24, 2012);</p><p>n.a. not available.</p

Genetic association between iron and ferritin levels and haplotype-pairs in <i>SLC11A2</i> and <i>TMPRSS6</i> in SAPHIR.

<p><u>Notes</u>: For the haplotype pairs in <i>SLC11A2</i> and <i>TMPRSS6</i>, the regression was performed on all haplotype pairs in one model with the most probable haplotype pair as the reference. For the combined analysis, each line reflects the results from a regression model of this particular haplotype-pair versus all other pairs on the traits (each model sex- and age-adjusted). The p-values are based on the log-transformed model; the β-estimates are based on the model on the original scale.</p

Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.

<p>Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.</p

Genetic risk score and the risk of TPOAb-positivity.

<p>GRS, genetic risk score (based on rs11675434, rs653178, rs10944479, rs1230666, rs2010099).</p>a<p>Adjusted for age and gender</p