Fig. 4: Pervasive nuclear genetic control over common mtDNA heteroplasmies.
From: Nuclear genetic control of mtDNA copy number and heteroplasmy in humans
a, Quality control (QC)-passing mtDNA heteroplasmies in UKB and AoU. From the inside: mtDNA positions of poly-C tracts; genomic annotations (orange, HVR; yellow, rRNA genes; blue, tRNA genes; purple, coding genes); heteroplasmic SNV counts (red); heteroplasmic indel counts (black). The teal arc region is the focus of Fig. 5. Line in outermost track, 100 indels. b, Mean heteroplasmy count per individual across age groups in AoU. Error bars are 1 s.e.m.; total n = 95,328. c, Heteroplasmy transmission in mother versus offspring (left), father versus offspring (middle) and sibling versus sibling (right) for UKB heteroplasmic variants. d, Heteroplasmy transmission in 1000G cell lines in mother versus offspring (left) and father versus offspring (right) pairs. e, Selected heteroplasmy distributions among carriers. For panels a–d, red, SNV; black, indels. f, GWAS lead SNPs from common heteroplasmies with any signals at GWS. Point size corresponds to lead SNP two-sided P value; dark points are at GWS. Vertical lines, SNPs identified for multiple mtDNA variants or near genes of interest. Green, genes also nominated for mtCN; *has Cauchy P value at GWS from RVAS; †CS variants with PIP > 0.1; ‡CS variants with PIP > 0.9; ‘c’, coding variant in CS; underline, eQTL colocalization with PIP > 0.1. g, Role of genes identified by heteroplasmy GWAS in mtDNA dynamics. h, chrM:16183:AC,A heteroplasmy versus DGUOK lead SNP genotype. i, Structure of DGUOK (2OCP from RSCB under CC0 license; https://doi.org/10.2210/pdb2ocp/pdb) with Q170 in red, nearby residues participating in hydrogen bonds or stacking interaction in pink, and dATP as black sticks. j, chrM:16183:A,AC heteroplasmy versus POLG2 lead SNP genotype. k, Structure of polymerase gamma (4ZTU from RSCB under CC0 license; https://doi.org/10.2210/pdb4ZTU/pdb) with POLG in light blue and POLG2 subunits in green/yellow. Bound DNA is in dark blue; POLG2 residue G416 is shown as red spheres. In panels h and j, red lines, median.
