We developed a novel method to estimate mtDNA-CN from genetic array data, “AutoMitoC”, and applied it to the UKBiobank study. Extensive genetic invesal key insights regarding mtDNA-CN.
First, several novel common and rare genetic determinants of mtDNA-CN were identified, totalling 73 loci. Second, these loci were enriched for mitochondrial processes related to dNTP metabolism and the replication, packaging, and maintenance of m; common variation within known mtDNA depletion genes in regulating mtDNA-CN in the general population. Fourth, we found that rare variants in SAMHD1 not only affect mtDNA-CN levels but also confer risk to cancer.
Finally, we provided the first Men Randomization evidence implicating low mtDNA-CN as a causative risk factor for dementia.