The Effects of Risk Genotypes of the <i>PPARG</i> P12A Polymorphism (PP), the Combination of <i>CAPN10</i> SNP43/44 (GG/TT), and the Combination of <i>PPARG</i> and <i>CAPN10</i> SNP43/44 (PP/GG/TT) Together with FPG and BMI for the Risk of Developing T2D

<p><i>y</i>-Axis denotes incident diabetes estimated as the proportion (percent) of participants who developed diabetes during the follow-up period in the groups with each risk factor defined as risk genotype, elevated FPG (≥5.6 mmol/l), and high BMI (≥30 kg/m²). The absolute number of individuals who developed diabetes in the groups with each risk factor is given within the bars (in parentheses) and in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020345#st002" target="_blank">Table S2</a>. The incidence of T2D was significantly increased in carriers of the risk PP genotype, GG/TT genotypes, and PP/GG/TT genotypes with elevated FPG and high BMI as compared with individuals carrying low risk genotypes without risk factors (χ² test, <i>p <</i> 0.001).</p

The Effect of Insulin Resistance Together with the Risk Genotype of the <i>PPARG</i> P12A Polymorphism on Risk of Developing T2D

<p><i>y</i>-Axis denotes HR and its 95% CI. <i>x</i>-Axis denotes increase in insulin resistance estimated as HOMA_IR.</p

Unadjusted Kaplan–Meier Diabetes-Free Survival Probability Curves

<p>Curves for different carriers of <i>PPARG</i> P12A (PP versus PA/AA), <i>CAPN10</i> SNP44 (TT versus TC/CC), <i>UCP2</i> −866 G/A (GG versus GA/AA), and the combination of <i>PPARG</i> and <i>CAPN10</i> SNP43/44 (PP/GG/TT versus other). <i>y-</i>Axis shows probability of diabetes-free survival time. <i>x</i>-Axis shows follow-up time in years. The HR of developing T2D in different genotype carriers obtained from Cox proportional hazards regression stratified on sex and adjusted for age, BMI, and family history of diabetes with robust variance estimate is shown (see also <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020345#pmed-0020345-t003" target="_blank">Table 3</a>).</p

Risk of incident CAD by rs4977574 stratified by smoking status.

<p>Adjusted for age and sex.</p><p>Daily cigs  =  number of daily cigarettes.</p

Smoking as a risk factor for CVD-mortality, stratified by number of rs4977574 risk alleles.

<p>Adjusted for age and sex.</p

CV mortality in males and females according to the <i>GYS1</i> XbaI (A) and <i>APOE</i> –219/ε2/ε3/ε4 (B) genotypes.

<p>Kaplan Meier survival curves illustrating a higher risk for CV mortality (HR 1.8 [1.2–2.6], p = 0.0016, p_c = 0.0096) in male carriers of the <i>GYS1</i> XbaI CT/TT-genotypes and in female carriers of the <i>APOE</i> –219TT/ε4 genotype combination (HR 2.3 [1.6–3.2], p<0.0001, p_c<0.0001).</p

CLINICAL AND GENETIC RISK FACTORS FOR CV MORTALITY

<p>Univariate Cox proportional-hazards analysis, performed with robust variance estimate to adjust for within family dependence. BMI; body mass index, WH; waist to hip ratio</p

Interaction between the <i>GYS1</i> XbaI polymorphism and physical activity (PA) in males.

<p>Kaplan Meier survival curves for males reporting normal to high physical activity (PA) level according to <i>GYS1</i> XbaI genotype compared to males with low PA level.</p

Meta analysis: Risk of incident CAD by Chromosome 9p21 stratified by smoking status.

<p>Hazard ratios (HR) with 95% Confidence Interval (CI) per Chromosome 9p21 risk allele in MDCS (rs4977574; N = 24944; 28% smokers) and ARIC (rs10757274; N = 9877; 25% smokers). Pooled HR per allele for incident CAD in non-smokers and smokers were 1.23 (95% CI 1.16–1.30) and 1.07 (95% CI 0.99–1.15) respectively. MDCS  =  Malmö diet and cancer study. ARIC  =  Atherosclerosis Risk in Communities Study.</p

GENOTYPE DISTRIBUTION IN SUBJECTS WHO DIED FROM CV CAUSES AND IN SUBJECTS WHO ARE ALIVE OR DIED DUE TO OTHER CAUSES

<p>Fischer's exact test, *p = 0.019 (p_c = 0.057), †p = 0.0038 (p_c = 0.011), ‡p = 0.00048 (p_c = 0.0014)</p