Distribution of 25-hydroxyvitamin D concentration by background, lifestyle and social characteristics in the 1958 British birth cohort.

<p>*Values are <i>n</i> (%) or geometric mean. <i>p</i>-values from test for trend in linear or logistic regression adjusted for season and sex. Unknown values excluded.</p><p>**Waist circumference quartiles: for men; 65.4–90.6, 90.7–96.7, 96.8–103.5, 103.6–151.2 cm; for women; 56.2–75.8, 75.9–82.6, 82.7–91.6, 91.7–138.3 cm.</p><p>†Classes I&II are managerial/professional, IV/V unskilled manual. “Other” includes cohort members who are institutionalised, retired, unemployed and other unclassifiable.</p

Variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E) by 25(OH)D concentration.

<p>Model 1 (solid line): adjusted for month of measurement and sex. Model 2 (dashed, short): adjusted for lifestyle and social indicators (physical activity, time spent watching TV/using PC, smoking, alcohol consumption and birth and adult social class), month of measurement and sex. Model 3 (dashed, long): adjusted for adiposity (BMI and waist circumference), lifestyle/social indicators, month of measurement, and sex. Values are coefficients from linear regression (reference <25nmol/l), 95% confidence intervals presented for Model 3 by the shaded area.</p

Seasonal variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E).

<p>Values are from the partial regression of the harmonic components; Model 1 (solid line) adjusted for respiratory infections, alcohol consumption, PC/TV time, physical activity and social class at birth and adulthood, and Model 2 (dashed line, shown with 95% confidence intervals) in addition to above adjusted for 25-hydroxyvitamin D. Tick marks denote average concentrations (SDS, predicted from random effects models) with 95% confidence intervals shown by error bars. Predicted means for CRP from linear models, no seasonal pattern observed (p>0.8). *p-values from the product of coefficient mediation test used to assess the 25(OH)D mediation effect on the seasonal patterns in the outcomes.</p

Variation in the average 25(OH)D concentration by body mass index (A) and waist circumference (B).

<p>Values are geometric means (95% confidence intervals) standardized by sex.</p

Strategy for SNP selection using genome-wide association and candidate gene studies.

<p>Strategy for SNP selection using genome-wide association and candidate gene studies.</p

Association between the SNPs, synthesis, metabolism and metabolism^GWA allele scores and ln 25(OH)D with and without adjustment for biomarkers, dietary and lifestyle indicators.

<p>The bars are the 95% CI. <i>Biomarkers</i>: coagulation markers- von Willebrand factor, tPA and D-dimer; Inflammatory markers- fibrinogen and CRP; Lipid marker- Triglycerides, low density lipoproteins, high density lipoproteins and total cholesterol; Lung function marker- FEV; Cardiovascular disease related factors- diastolic and systolic blood pressures, IgE, IGF1 and HbA1c). <i>Dietary and lifestyle markers</i>: time spent outside, sun cover, oily fish consumption, vitamin D supplements, season, smoking, alcohol consumption, PC/TV time, recreational MET hours, social class, body mass index, abdominal obesity and geographical region.</p

Association of SNP with ln 25-hydroxyvitamin D adjusted for sex.

<p>MAF, minor allele frequency.</p>†<p>Relative bias has not been estimated where the SNP has an F-statistic less than 1.9.</p

The selection of vitamin D SNPs for the use as instruments in Mendelian Randomization (MR) analysis.

<p>The selection of vitamin D SNPs for the use as instruments in Mendelian Randomization (MR) analysis.</p

Associations of the five SNPs and allele scores with geographical region, social, dietary and lifestyle factors.

<p>The bars are the 99.6% CI. The effects of the allele scores and the individual SNPs for each lifestyle factor can be identified based on the intensity of the coloured boxes.</p

Power and sample size to detect the 5% decrease in blood pressure by 10 nmol/l increase in 25(OH)D observed in the 1958 British birth cohort using genetic proxy indicators (significance level α = 0.05).

<p>The curves in (<b>A</b>) from the bottom to the top of the graph are in the order of min effect size with <i>CYP27B1</i> (short dash), <i>CYP24A1</i> (long dash), <i>DHCR7</i> (dash dot), <i>CYP2R1</i> (dash), <i>GC</i> (dot). The curves in (<b>B</b>) from the bottom to the top of the graph are in the order of min effect size with Synthesis score (dash dot), Metabolism^GWA score (long dash) Metabolism score (dash), both scores (dot). The horizontal black line and attached vertical dashed lines indicate the sample size required for a study with 80% power using the genetic proxy.</p