Relative mRNA expression of replicated genes in three calcium-transporting tissues (kidney, duodenum, tibia).

<p>The expression (based on delta CT [cycle threshold] normalized to actin) of the selected genes is compared to the expression of the <i>CASR</i> gene in the duodenum, thereby providing a relative expression. Cut-off was set at delta CT≤15. Data are means ± standard error of the mean (SEM) of values obtained from 5 mice fed a normal diet. <i>GCKR</i> was not expressed.</p

Genome-wide association for serum calcium in discovery analysis in Europeans.

<p>Manhattan plot showing −log₁₀(P values) for all SNPs in the discovery GWAS for uncorrected serum calcium in Europeans (N = 39,400), ordered by chromosomal position. The plot is truncated at −log10 P values of 10 (truncated −log₁₀P values for GCKR and CASR). The values correspond to the association of uncorrected serum calcium, including age and sex as covariates in the model as well as study-specific covariates if needed. The gene closest to the SNP with the lowest P value is listed at each locus. Six loci reached genome-wide significance (<i>P</i><5E-08) at discovery analysis (<i>GCKR</i>, <i>DGKD</i>, <i>CASR</i>, <i>VKORC1L1</i> (in grey on chromosome 7), <i>CARS</i> and <i>CYP24A1</i>. The seven loci that reached genome-wide significance at the combined analysis following replication are highlighted in red (<i>GCKR</i>, <i>DGKD</i>, CASR, <i>GATA3</i>, <i>CARS</i>, <i>DGKH</i>-KIAA0564 and <i>CYP24A1</i>).</p

Relative mRNA expression of identified genes from mice fed a low (0.17%) and high (1.69%) calcium diet compared to mice fed a normal calcium diet (0.82%).

<p>Data are means± SEM of values obtained from 5 mice for each diet group. Expression levels were normalized to actin. Statistical significance of the difference between diets was calculated using unpaired t-test. *: <i>P</i>≤0.05 (low compared to high); §: <i>P</i>≤0.05 (low compared to normal); # <i>P</i>≤0.05 (high compared to normal).</p

Relative mRNA expression of identified genes in kidney tubule segments.

<p>The renal tubular segments analyzed were the proximal tubule (PROX), the thick ascending limb of the loop of Henle (TAL), the distal convoluted tubule and connecting tubule (DCT-CNT), and the cortical collecting duct (CCD). The expression (based on the delta CT [cycle threshold]) of the selected genes is compared to the expression of the <i>CASR</i> gene in the PROX, thereby providing a relative expression. Data are means of values obtained from 3 mice fed a normal diet. <i>GCKR</i> was not expressed.</p

Genome-wide significant and replicated loci for serum calcium in Europeans.

<p>P values are corrected for inflation using genomic control. Replication criteria: overall genome-wide significance (<i>P</i><5E-8) and one-sided replication <i>P</i><0.05. I² was zero for rs1801725, rs1550532, rs10491003, rs7336933 and rs1570669 (I²<i>P</i>>0.20). For rs780094 and rs7481584, I² were 0.79 and 0.43 with I²<i>P</i> 0.03 and 0.19, respectively. For these latter SNPs, sample size weighted meta-analysis P values were 2.93E-10 and 2.03E-10, respectively.</p><p>Chr, chromosome. Effect A1 = beta regression coefficient for allele A1; SE, standard error.</p>*<p>one-sided P values.</p

Look-ups of serum calcium loci with related phenotypes: bone mineral density in the GEFOS dataset [6] and endocrine phenotypes from the SHIP, SHIP Trend and SUNLIGHT [7] datasets.

<p>NA, not available. P values<0.05 were considered as statistically significant. A1, effect allele. β, regression coefficient for allele A1, SE, standard error. P, two-sided P value. Zscore, z score.</p