Top Significant SNP-associations with mtDNA Levels in GAIT.

<p>Chr.: Chromosome.</p>†<p>Minimal Allele Frequency of the SNP in our sample.</p>‡<p>represents the effect of one copy of the rare allele in mtDNA levels when it is expressed in original scale.</p>*<p>P-value of the association with mtDNA levels.</p>(a)<p>indicates statistical significance after Bonferroni correction for multiple testing.</p>(b)<p>indicates statistical significance after B-H adjustment for multiple testing assuming a 10% of false discovery rate.</p

Phenotypic Characteristics of the 386 Subjects Included in the GAIT Project.

†<p>Subjects in the study were defined as currently smokers when they smoke independently of the number of cigarettes.</p>‡<p>Oral contraceptives use at inclusion.</p>§<p>mtDNA levels were expressed as the mtDNA to nuclear DNA ratio (mtDNA/nDNA).</p><p>SD: standard deviation.</p><p>NS: not significant.</p>*<p>P-value<0.05 was considered statistically significant.</p

Linkage analysis for mtDNA levels in males only.

<p>The linkage signal detected in Chromosome 2 in the first analysis including the subjects of both sexes completely disappears in the analysis performed with males only. However, a new significant linkage signal for mtDNA levels is detected in Chromosome 1 only in males (LOD score of 2.81). Fine-mapping in this linkage region with 971 SNPs reveals the most significant SNP association with mtDNA levels for the rs10888838 (MAF = 0.1133; p = 4.01e-06) in the analysis with males only. This SNP was located in the gene <i>MRPL37</i>, which emerges as a strong candidate gene for the control of mtDNA levels in males.</p

Candidate Genes Proposed for Sex-specific Variation of mtDNA Levels in GAIT.

<p>Chr.: Chromosome.</p

Linkage analysis for mtDNA levels in females only.

<p>The linkage signal detected in Chromosome 2 in the first analysis including the subjects of both sexes remains in the analysis performed with females only. However, this linkage signal in the sex-specfic analysis becomes better defined and more significant (LOD score of 3.09; p = 8.11e-05). In addition, a new quantitative trait locus for mtDNA levels is detected in Chromosome 3 only in females (LOD score of 2.67; p = 2.27e-04). Fine-mapping of the female-specific QTLs detected on Chromosome 2 and Chromosome 3 was carried with a set of 790 and 2687 SNPs, respectively.</p

Linkage analysis for mtDNA levels in subjects of both sexes.

<p>There is a linkage signal in Chromosome 2 with a peak LOD score of 2.21 (p = 7.09e-04) defining a quantitative trait locus for mtDNA levels in a region that maps to 2p25.3-2p24.3.</p

Data of the Linkage Analysis for mtDNA Levels in GAIT.

<p>Chr.: Chromosome.</p>*<p>This Chromosome position refers to the linkage signal from the analysis using all of the subjects. Chromosome position for the linkage signal detected in Chromosome 2 only in females is 2p25.3-2p25.1. All Chromosome positions were based on the National Center for Biotechnology Information (NCBI) build 36.</p

Summary of the four statistically significant SNPs on a genome-wide level.

<p>LD estimates were based on founders alone.</p>(1)<p>MAF: minor allele frequency based only on founders;</p>(2)<p>β: effect size on PC (for rs867186 and rs8119351) and PS (for rs1413885 and rs1570868) plasma levels per minor allele (standard deviation scale);</p>(3)<p>R²: proportion of variance explained by each SNP assuming lack of LD.</p

Top ten SNP associations for PC, fPS, funcPS and total PS plasma levels.

<p>An asterisk in the p-value indicates significance after B-H adjustment for multiple comparisons.</p