Genetic and observational estimates of the influence of altering BMI on serum testosterone (T).

<p>Effect sizes are given in percent change in serum T based on a decrease in BMI from 30 (cut off for obesity) to 25 (cut off for overweight) kg/m² (n = 7446). _wGRS_BMI = weighted genetic risk score on BMI. _uwGRS_BMI = un-weighted genetic risk score on BMI. Horizontal bars represent 95% confidence intervals.</p

Characteristics of the cohorts.

<p>Characteristics of the cohorts.</p

Observational estimates.

<p>An increased BMI is associated with a decreased serum testosterone (T). Linear regression models were used adjusting for age, smoking, site and time of day for blood sample, when applicable. The combined effect was calculated with random effect meta-analysis (I-squared = 82%, p = 0.0005) using all cohorts (n = 7446). Effect sizes are given in standard deviations (SD) of T per SD ln-transformed BMI. Horizontal bars represent 95% confidence intervals.</p

Summary of the coefficients used for IV ratio analyses.

<p>Summary of the coefficients used for IV ratio analyses.</p

Characteristics of the cohorts included in the discovery GWA meta-analyses and replications.

<p>Position = Position of section in proximal direction from distal end of tibia.</p><p>vBMD = volumetric bone mineral density; NA = not available.</p

Association of cortical and trabecular vBMD with top cortical and trabecular vBMD SNPs.

<p>Models adjusted for sex (ALSPAC and YFS), age, height, weight (ln). Betas in standard deviations and standard errors are presented. vBMD = volumetric bone mineral density; EAF = effect allele frequency; n^GEFOS and P^GEFOS is the number of subjects and p values as given from the GEFOS consortium (<a href="http://www.gefos.org/?q=content/data-release" target="_blank">http://www.gefos.org/?q=content/data-release</a>; <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003247#pgen.1003247-Estrada1" target="_blank">[2]</a>). Dir = Direction of the effect in the GEFOS publication using the same effect allele as in the present pQCT meta-analysis.</p

Regional association plots for the 5 independent signals from the discovery genome-wide meta-analysis of cortical vBMD.

<p>(A) rs1021188, (B) rs271170, (C) rs7839059, (D) rs6909279, (E) rs17638544. Circles show the GWA meta-analysis p-values, with different colors indicating varying linkage disequilibrium with the indicated SNP (diamond). SNPs in the same region identified in a recent large-scale GWA meta-analysis of aBMD are indicated by a red outer circle <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003247#pgen.1003247-Estrada1" target="_blank">[2]</a>. LocusZoom: <a href="http://csg.sph.umich.edu/locuszoom/" target="_blank">http://csg.sph.umich.edu/locuszoom/</a>.</p

The associations of the SNPs explaining most of the cortical vBMD (rs1021188) and trabecular vBMD variations (rs9287237), respectively, with bone parameters in the GOOD cohort at the follow-up visit (n = 729).

<p>Mean and standard error z-scores are shown for trabecular and cortical vBMDs as analyzed by pQCT, and for trabecular bone volume per total volume (BV/TV), trabecular number (TbN), trabecular thickness (TbTh), trabecular separation (TbSp) and cortical porosity as analyzed by HRpQCT.</p

Characteristics of the GOOD five year follow-up cohort.

<p>vBMD = volumetric bone mineral density; BV/TV = bone volume per total volume; TbN = trabecular number; TbTh = trabecular thickness; TbSp = trabecular separation.</p

The genome-wide meta-analyses according to sex.

<p>(A) Cortical vBMD (<i>rs1021188</i> effect allele = C, <i>rs271170</i> effect allele = T, <i>rs7839059</i> effect allele = A, <i>rs6909279</i> effect allele = G, <i>rs17638544</i> effect allele = T). (B) Trabecular vBMD for <i>rs9287237</i> (effect allele = T). Mean and standard error vBMD z-scores are shown for each cohort, stratified by sex. Diamonds show the combined z-scores estimates per genotype (the width of the diamond represents the combined standard error). Disc = discovery cohort, repl = replication cohort.</p