The UGT1A1 interaction network generated using the Ingenuity Pathway Analysis.

<p>The molecular relationships connecting UGT1A1 to DNA metabolism synthesis, fragmentation and quantity of DNA are indicated with Fx symbols, and the associated Canonical Pathways are indicated with CP symbols. Abbreviations: AHR, aryl hydrocarbon receptor; HMGB1, high-mobility group box protein 1; IL1B, interleukin-1 beta; MYC, v-myc myelocytomatosis viral oncogene homolog; NR1I3, nuclear receptor subfamily 1, group I, member 3; PPARGC1A, peroxisome proliferator –activated receptor gamma coactivator 1 alpha; RELA, v-rel reticuloendotheliosis viral oncogene homolog A (avian); TLR4, Toll-like receptor 4.</p

IV approach, study sample (N = 753), women (N = 479), men (N = 274).

<p>Significant at **5%, and</p><p>***1% level.</p><p>Heteroskedasticity-robust standard errors are shown in the parentheses.</p><p>Total steps and aerobic steps are transformed with natural logs.</p><p>Two model specifications, one without control variables, excluding age (Model 1), and one with full set of control variables (Model 2). Added control variables: the vector of socioeconomic characteristics and health status observed in 2007, and family background factors observed in 1980.</p><p>Instruments used: Income, obtained in 2007 and household income obtained in 1980.</p><p>Because the Sargan test is not available with cluster robust standard errors, the test was executed with non-robust errors. Thus, the results should be treated with a care.</p><p>IV approach, study sample (N = 753), women (N = 479), men (N = 274).</p

Characteristics of the study population.

*<p>Median values and interquartile range (IQR), Mann-Whitney test for between-group differences.</p>†<p>Chi-squared test for differences between groups.</p><p>Abbreviations: BMI,body mass index; cf-DNA, cell-free DNA; COCs, combined oral contraceptives; CRP, C-reactive protein; N.S., not significant.</p

The top SNPs in each of the 9 sub-blocks in the <i>UGT1A</i> gene region (see Figure 2).

<p>The four SNPs that are associated most significantly with serum cf-DNA levels are in sub-block 8.</p>†<p>For each SNP, the ancestral allele was modelled, and the β coefficient represents the change in cf-DNA level (µg/ml) with one additional copy of the ancestral allele.</p>*<p>Adjusted for age, sex, BMI and genetic East-West stratification in the Finnish population.</p><p>Abbreviations: SNP, single nucleotide polymorphism; Chr, chromosome; bp, base pairs; MAF, minor allele frequency; S.E., standard error.</p

Correlation between different physical activity measures among women (N = 479) and among men (N = 274).

<p>*** Significance at the 1% level.</p><p>Correlation between different physical activity measures among women (N = 479) and among men (N = 274).</p

Scatterplot of serum lipoprotein longitudinal profiles of participants according to their sex and wGRSs status (High and Low wGRS*) (N = 2435, N = 2308 and N = 2435 for LDL-C-, HDL-C- and triglyceride profiles respectively).

<p>Solid and dotted lines represent estimated sex-specific average age-related lipid trajectories for participants in High and Low genetic risk score, respectively (i.e. prototypical growth curves); grey bands around the growth curves represent approximated 95% prediction CI. Overlaid with the prototypical lipid trajectories are the age-specific cut points for lipoprotein status (normal vs. high risk) as defined by the NCEP adolescent and childhood classification [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146081#pone.0146081.ref036" target="_blank">36</a>] and NCEP adult-treatment panel guidelines [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0146081#pone.0146081.ref037" target="_blank">37</a>]). The cut points are represented in grey/white blocks, used to identify those at significantly increased risk of developing atherosclerotic CVD in adulthood. * Mid wGRS risk group are not presented on the figure for the purpose of readability.</p

Age- and sex- stratified estimated effects of LDL-C wGRS (upper panel), HDL-C wGRS (middle panel) and TG wGRS (lower panel) on LDL-C, HDL-C and triglycerides levels respectively with color coded significance levels and studentized bootstrapped non-parametric 95% CI.

<p>For each age, the continuous error bars correspond to males and the dashed error bars directly next to them correspond to female models. Effect sizes are in mmol/L change per 1-sd change in wGRS for LDL-C and HDL-C and in odds ratio lipoprotein level change per 1-sd change in wGRS for triglycerides. Point sizes of the beta estimates reflect sample size (number of participants included in each age- and sex-specific regression analysis) Parameter estimates significance: Lightgrey, 0.05-3-6; Black, p-val≤1.X10^-6. Black lines: smooth trend curves fitted by LOESS (Locally weighted non-parametric regression) to help visualise trends in the cross-sectional associations.</p

Sex-specific marginal effect* and 95% CI of (A) combined continuous HDL-C wGRS on HDL-C levels (effect size expressed in mmol/L lipoprotein level change per 1-sd change in wGRSs); and (B) combined continuous TG wGRS on fasting triglyceride levels (effect size expressed in odds ratio lipoprotein level change per 1-sd change in wGRSs).

<p>Colour code: dark grey; females, light grey; males. (*Plotted marginal effect includes the significant linear slope, quadratic and quartic rates of change (cubic trajectory parameter not significant in the final model); Horizontal black dashed line shows where the slopes are not significantly different from zero).</p

El Diario de Pontevedra : periódico liberal: Ano XXIV Número 7068 - 1907 novembro 9

Results of mixed models with age as a categorical predictor and log-insulin as a continuous predictor: LS means contrasts (No adult T2DM vs. adult T2DM) and significance at each age averaged over- (Table S1.) or adjusted for the levels of sex (Table S2.) and pairwise comparisons of Least-square means of BMI and 95% CIs at each age in each T2DM status group averaged over levels of sex (Figure S1.) at each age in each T2DM status group and sex group combination (M = males, F-females, 1 = No adult T2DM, 2 = adult T2DM) (Figure S2.) and adjusted for log(insulin). (DOCX 549 kb

sj-docx-2-sjp-10.1177_14034948221119611 – Supplemental material for Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study

Supplemental material, sj-docx-2-sjp-10.1177_14034948221119611 for Exposure to parental smoking and cardiac structure and function in adulthood: the Cardiovascular Risk in Young Finns Study by Jukka Pihlman, Joel Nuotio, Suvi Rovio, Katja Pahkala, Saku Ruohonen, Eero Jokinen, Tomi P. Laitinen, David P. Burgner, Nina Hutri-Kähönen, Päivi Tossavainen, Leena Taittonen, Mika Kähönen, Jorma S.A. Viikari, Olli T. Raitakari, Costan G. Magnussen and Markus Juonala in Scandinavian Journal of Public Health</p