CpG sites analyzed in the <i>PPARGC1A</i> promoter.

<p>The CpG sites investigated are marked with a perpendicular line.</p

Clinical characteristics of the FDR group (n = 124) stratified according to glucose tolerance status.

<p>Data are mean ± SD. Significant differences between NGT and IFG/IGT at *<i>P</i><0.05. **<i>P</i><0.001. Significant differences between NGT and T2D at ⁺<i>P</i><0.05, ⁺⁺<i>P</i><0.001. Significant differences between IFG/IGT and T2D at ^§<i>P</i><0.05, ^§§<i>P</i><0.001. All parameters except age and BMI were analyzed with unpaired non-parametric tests due to lack of normal distribution. Indices of insulin sensitivity and insulin secretion were calculated as described in subjects and methods. BMI, body mass index; CIR, corrected insulin response; HOMA-β, homeostatic model assessment of β-cell function; HOMA-IR, homeostatic model assessment of insulin resistance; IFG, impaired fasting glycemia; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; T2D, type 2 diabetes.</p

Correlation between average skeletal muscle DNA methylation and gene expression of <i>PPARGC1A</i>.

<p>Methylation is show in percentage and gene expression in arbitrary units (AU). β = 0.013 (−0.034;0.059), <i>P = </i>0.59, adjusted for age, gender, BMI, glucose tolerance and family pedigree. Unadjusted (Spearman’s correlation): ρ 0.22, <i>P</i> = 0.04.methylation at CpG site −260 in the <i>PPARGC1A</i> promoter was 0% in 98 individuals and 4–10% in 11 individuals (4 with T2D and 7 with NGT). The DNA methylation at CpG site −260 was not different among T2D (1.1±1.7) compared to NGT subjects (0.74±2.3), and there were no significant associations between DNA methylation and whole body insulin sensitivity, gene expression or any other clinical parameter (data not shown).</p

Skeletal muscle gene expression of <i>PPARGC1A</i>.

<p>Participants are stratified according to glucose tolerance status (NGT, IFG/IGT, T2D). Data are mean±SE.</p

Meta-analysis of the effect of the C-allele of <i>TMEM154</i>-rs6813195 on insulinogenic index in 6,486 individuals from the Inter99 study (n = 5,181), Health 2008 study (n = 592), ADIGEN controls (n = 246), ADIGEN obese cases (n = 165) and Danish Family study (n = 302).

<p>Gray diamond represents combined change per risk allele and the 95% confidence interval. Gray squares represent effects size estimates (beta coefficients) in single studies sized according to their weight in the meta-analyses. The horizontal lines through the gray squares represent the 95% confidence interval. ob, obese. <i>p</i>, <i>P</i>-value. CI, confidence interval. W(fixed), study weight in the fixed effect meta-analysis.</p

Meta-analysis of the effect of the G-allele of <i>FAF1</i>-rs17106184 on 2-hour serum insulin in 6,260 individuals from the Inter99 study (n = 5,547), ADIGEN controls (n = 246), ADIGEN obese cases (n = 165) and Danish Family study (n = 302).

<p>Gray diamond represents combined change per risk allele and the 95% confidence interval. Gray squares represent effects size estimates (beta coefficients) in single studies sized according to their weight in the meta-analyses. The horizontal lines through the gray squares represent the 95% confidence interval. ob, obese. <i>p</i>, <i>P</i>-value. CI, confidence interval. W(fixed), study weight in the fixed effect meta-analysis.</p

T2D case-control analyses of up to 5,777 patients from Inter99 (n = 320), Health 2006 (n = 166), Health 2008 (n = 18), Steno Diabetes Center (n = 1,424), ADDITION (n = 1,870) and Vejle Biobank (n = 1,979) and up to 7,956 individuals with normal fasting glucose from Inter99 (n = 4,590), Health 2006 (n = 2,412), Health 2008 (n = 528) and Vejle Biobank (n = 426).

<p>Number of cases vs. number of controls is shown as 0/1/2 risk alleles. Odds ratios (OR) and <i>P</i>-values (<i>P</i>) are adjusted for age and sex. OR_adjBMI and <i>P</i>_adjBMI are adjusted for age, sex and BMI. SNP, single nucleotide polymorphism. RA, risk allele. RAF, risk allele frequency. CI, confidence interval.</p><p>T2D case-control analyses of up to 5,777 patients from Inter99 (n = 320), Health 2006 (n = 166), Health 2008 (n = 18), Steno Diabetes Center (n = 1,424), ADDITION (n = 1,870) and Vejle Biobank (n = 1,979) and up to 7,956 individuals with normal fasting glucose from Inter99 (n = 4,590), Health 2006 (n = 2,412), Health 2008 (n = 528) and Vejle Biobank (n = 426).</p

Meta-analysis of the effect of the C-allele of <i>TMEM154</i>-rs6813195 on disposition index in 6,486 individuals from the Inter99 study (n = 5,181), Health 2008 study (n = 592), ADIGEN controls (n = 246), ADIGEN obese cases (n = 165) and Danish Family study (n = 302).

<p>Gray diamond represents combined change per risk allele and the 95% confidence interval. Gray squares represent effects size estimates (beta coefficients) in single studies sized according to their weight in the meta-analyses. The horizontal lines through the gray squares represent the 95% confidence interval. ob, obese. <i>p</i>, <i>P</i>-value. CI, confidence interval. W(fixed), study weight in the fixed effect meta-analysis.</p

Associations between the seven T2D risk variants and quantitative traits in up to 5,744 Danish individuals naive to glucose-lowering medication.

<p>Raw data are mean±SD or median (interquartile range) and are stratified according to genotype. Values of serum insulin and derived indexes of insulinogenic index, ISI_Matsuda, disposition index and BIGTT-AIR were natural logarithmical (ln) transformed before analysis. Effects represent beta coefficients and are shown for the T2D risk allele. <i>P</i>-values (<i>P</i>) are adjusted for age (BIGTT-AIR and BIGTT-SI) or sex and age (all other traits). <i>P</i>_adjBMI are <i>P</i>-values adjusted for age, sex and BMI. All analyses assume an additive genetic model. SE, standard error.</p><p>Associations between the seven T2D risk variants and quantitative traits in up to 5,744 Danish individuals naive to glucose-lowering medication.</p