We investigated the concordance of mitochondrial DNA heteroplasmic mutations (heteroplasmies) in different types of maternal pairs (n=6,745 pairs) of European (EA, n=4,718 pairs) and African (AA, n=2,027 pairs) Americans with whole genome sequences (WGSs). The average concordance rate of heteroplasmies was highest between mother-offspring pairs, followed by sibling-sibling pairs and more distantly related maternal pairs in both EA and AA participants. The allele fractions of concordant heteroplasmies exhibited high correlation (R2=0.8) between paired individuals. Compared to concordant heteroplasmies, discordant ones were more likely to locate in coding regions, be nonsynonymous or nonsynonymous-deleterious (p<0.001). The average number of heteroplasmies per individual (i.e. heteroplasmic burden) was at a similar level until older age (70-80 years old) and increased significantly thereafter (p<0.01). The burden of deleterious heteroplasmies (combined annotation-dependent depletion score≥15), however, was significantly correlated with advancing age (20-44, 45-64, ≥65 years, p-trend=0.01). A genome-wide association analysis of the heteroplasmic burden identified many significant (P<5e-8) common variants (minor allele frequency>0.05) at 11p11.12. Many of the top SNPs act as strong long-range cis regulators of protein tyrosine phosphatase receptor type J. This study provides further evidence that mtDNA heteroplasmies may be inherited or somatic. Somatic heteroplasmic variants increase with advancing age and are more likely to have an adverse impact on mitochondrial function. Further studies are warranted for functional characterization of the deleterious heteroplasmies occurring with advancing age and the association of the 11p11.12 region of the nuclear genome with mtDNA heteroplasmy. ### Competing Interest Statement The authors have declared no competing interest.

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