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Fig. SI. Type I error rates estimated when inline image = 0% at α = 0.001 for inline image. The y-axis is plotted on a log10 scale, therefore, 0.001, 0.002, 0.003, 0.004, 0.005 correspond to −3.0, −2.70, −2.52, −2.40, and −2.30 on the log10 scale, respectively. The five strategies were as follows: (1) UI, only unrelated individuals (i.e., founders or singletons) were analyzed using linear regression. (2) NF, all individuals were included and familial correlation (Figure 1A) was accounted for in a linear mixed effects (LME) model. (3) MO, fathers were excluded. Mother and offspring were used for analysis. This reduced covariance structure (without father in Figure 1A or 1B) could be accommodated by LME. (4) ML, all individuals were used to define maternal lineages and random effect of lineages were accounted for in a LME model. (5) BO, all individuals were included and families were used as a cluster as in strategy NF. However, both coefficient structures of nDNA (Figure 1A) and mtDNA (Figure 1B) were accounted for in a LME model in families.

Fig. SII. Type I error rates estimated when inline image = 0% at α = 0.001 for inline image. The y-axis is plotted on a log10 scale. Therefore, 0.001, 0.0001, and 0.0001 correspond to −3.0, −4, and −5 on the log10 scale, respectively. Please see footnote in Figure 2 for description of the analytical strategies. In the parentheses of the legend, “M” stands for maternal permutation or PERMM and “F-M” stands for father-mother pair permutation or PERMF-M.

Fig. SIII. Power estimated using αPERM_F_M_0.001 and αPERM_M_0.001 when inline image. Please see footnote in Figure 2 for description of the analytical strategies. In the parenthesis of the legend, “M” stands for maternal permutation or PERMM and “F-M” stands for father-mother pair permutation or PERMF-M.

Fig. SIV. Observed P values for association analysis of 107 mitochondrial variants using the Framingham Heart Study data. The x-axis is base pair position. SBP, systolic blood pressure; DBP, diastolic blood pressure; FBG, fasting blood glucose.

Table S1. Power for unrelated individuals

Table S2. Power for samples with only mother and three offspring

Table S3. Information for the 196 SNPs which were genotyped in the Framingham Heart Study offspring cohort

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