Additional file 1: Figure S1. of Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness

Frequency of positive BH4-loading test is higher in mildest PKU phenotypes. Error bars represent the 95 % confidence intervals. Fisher exact test, ***p ≤ 0.001, **p ≤ 0.01, *p ≤ 0.05. (TIF 32 kb

Estimates of familial correlations ± standard error for serum haptoglobin concentration (656 familles/2680 individuals).

<p>* <i>P</i>≤0.05, ** <i>P</i>≤0.01, *** <i>P</i>≤0.001: compared to zero.</p><p>Model 1 estimated all eight correlations without adjustment.</p><p>Model 2 estimated all eight correlations with adjustment for age and BMI,</p><p>Model 3 estimated three correlations with adjustment for age and BMI with no gender effect on parent or offspring correlations: FS = MS = MD = FD and SS = SD = DD.</p><p>Model 4 estimated three correlations with adjustment for age, BMI and rs2000999 allelic frequency with no gender effect on parent or offspring correlations: FS = MS = MD = FD and SS = SD = DD.</p><p>Values in brackets were constrained to be equal to a preceding value according to the hypotheses of the model.</p><p>BMI: body mass index.</p

Discovery and replication of rs2000999 association data for Hp levels.

<p>N: sample size; MAF: Minor Allele Frequency; β:beta coefficient for the effect allele A.</p

Variance components of serum haptoglobin concentrations (656 families/2680 individuals, rs2000999 & rs4788597 as allelic frequency).

*<p><i>P</i>≤0.05,</p>**<p><i>P</i>≤0.01,</p><p>*** <i>P</i>≤0.001.</p><p>BMI: body mass index.</p

Manhattan plot of the GWAS of the discovery cohort comprising 631 children.

<p><b>A</b>, A Manhattan plot showing the −log₁₀(<i>P</i> values) of SNPs from the association analysis of the 631 SFS children from stage 1. <b>B</b>, An overview of the −log₁₀(<i>P</i> values) of Chromosome 16. <b>C</b>, The genomic region of the 618 LD block displayed in UCSC Genome Browser.</p

Phenotypic characteristics of the studied populations.

<p>CI: confidence interval; BMI: body mass index; LDL: low-density lipoprotein.</p