Cohort and sex-specific characteristics of studies included in the analysis of the association between birth weight and later risk of coronary heart disease.

<p>Cohort and sex-specific characteristics of studies included in the analysis of the association between birth weight and later risk of coronary heart disease.</p

Distribution of individuals and of CHD-events by sex and birth weight.

<p>Distribution of individuals and of CHD-events by sex and birth weight.</p

Risk of coronary heart disease according to birth weight and BMI at age seven years.

<p>The estimates are adjusted for sex and cohort (Danish or Finnish), estimated by Cox regression with age as the underlying time scale. The lines join points with the same hazard ratio for CHD and are truncated to depict the inner 98% of the BMI distribution. Arrows indicate median values, the plus indicates the risk at the joint median and the M indicates the minimum risk.</p

Risk of coronary heart disease in adulthood according to BMI at age seven years.

<p>The estimates are adjusted for sex and cohort (Danish or Finnish), estimated by Cox regression based on restricted cubic splines with age as the underlying time scale and truncated to depict the inner 98% of the BMI distribution. The dashed line shows the estimates without adjustment for birth weight, the bold line shows the estimates with adjustment for birth weight and the dotted lines show the 95% confidence limits for the adjusted estimates.</p

Regional association plots showing genome-wide significant loci for serum TSH.

<p>In each panel (A–F), the most significant SNP is indicated (purple circle). The SNPs surrounding the most significant SNP are color-coded to reflect their LD with this SNP as in the inset (taken from pairwise r² values from the HapMap CEU database build 36/hg18). Symbols reflect genomic functional annotation, as indicated in the legend <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003266#pgen.1003266-Pruim1" target="_blank">[61]</a>. Genes and the position of exons, as well as the direction of transcription, are noted in lower boxes. In each panel the scale bar on the Y-axis changes according to the strength of the association.</p

Regional association plots showing genome-wide significant loci for serum FT4.

<p>In each panel (A–F), the most significant SNP is indicated (purple circle). The SNPs surrounding the most significant SNP are color-coded to reflect their LD with this SNP as in the inset (taken from pairwise r² values from the HapMap CEU database build 36/hg18). Symbols reflect genomic functional annotation, as indicated in the legend <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003266#pgen.1003266-Pruim1" target="_blank">[61]</a>. Genes and the position of exons, as well as the direction of transcription, are noted in lower boxes. In each panel the scale bar on the Y-axis changes according to the strength of the association.</p

Regional association plots showing genome-wide significant loci for serum TSH.

<p>In each panel (A–F), the most significant SNP is indicated (purple circle). In panel F, an independent signal at the associated locus is indicated with an arrow. The SNPs surrounding the most significant SNP are color-coded to reflect their LD with this SNP as in the inset (taken from pairwise r² values from the HapMap CEU database build 36/hg18). Symbols reflect genomic functional annotation, as indicated in the legend <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003266#pgen.1003266-Pruim1" target="_blank">[61]</a>. Genes and the position of exons, as well as the direction of transcription, are noted in lower boxes. In each panel the scale bar on the Y-axis changes according to the strength of the association.</p

TSH associated SNPs in extreme phenotype categories.

<p>The table shows results for the quartile-based GRS scores (top panel) and single marker (bottom panel) analyses in extreme phenotype categories, defined as TSH >4 mIU/L (UPPER) or TSH <0.4 mIU/L (LOWER). NORMAL, individuals with TSH within the normal range. OR, odds ratio; StdErr, standard error. A1, effect allele; A2 other allele. SNPs reaching the Bonferroni significance threshold are highlighted in bold.</p

Independent SNPs associated with TSH and FT4 serum levels.

<p>The table shows the association results for SNPs that reached genome-wide level (p<5×10⁻⁰⁸) in the main meta-analysis. SNPs at <i>LPCAT2/CAPNS2</i> and <i>NETO1/FBXO15</i> reached the GW threshold in the gender-specific meta analysis (see <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003266#pgen-1003266-t003" target="_blank">Table 3</a>), and here the p-value in the main meta-analysis is reported. For each SNP, the best candidate gene is showed, as well as its genomic position in build 36, the effect allele (A1) and the other allele (A2), its combined frequency across studies and its standard error, the effect size and its standard error, the p-value for association, the number of samples analyzed, and the p-values for heterogeneity of effects across the cohorts meta-analyzed. Effect sizes are standardized, so they represent the estimated phenotypic change, per each copy of the effect allele, in standard deviation units.</p

Regional association plots showing genome-wide significant loci for serum TSH.

<p>In the upper panel, the most significant SNP is indicated (purple circle). The SNPs surrounding the most significant SNP are color-coded to reflect their LD with this SNP as in the inset (taken from pairwise r² values from the HapMap CEU database build 36/hg18). Symbols reflect genomic functional annotation, as indicated in the legend <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1003266#pgen.1003266-Pruim1" target="_blank">[61]</a>. Genes and the position of exons, as well as the direction of transcription, are noted in the lower box. The scale bar on the Y-axis changes according to the strength of the association.</p