Genome-wide association study

For mtDNA variants calling, referring to the supplementary methods:

"DNA extraction and genotyping were performed on saliva samples by National Genetics Institute (NGI), a CLIA licensed clinical laboratory and a subsidiary of Laboratory Corporation of America. The platform was a fully customized array with additional coverage of lower-frequency coding variation, and about 570,000 SNPs. Samples that failed to reach 98.5% call rate were re-analyzed. Individuals whose analyses failed repeatedly were re-contacted by 23andMe customer service to provide additional samples."

We used a custom Illumina custom Array (v4). Genotype calls are made using Illumina's Genome Studio software.

For mtDNA copy number estimates, papers from the literature suggest using median log-R ratio (Longchamps et al. 2020 https://doi.org/10.1371/journal.pone.0228166; Castellani et al. 2020 https://doi.org/10.1186/s13073-020-00778-7). Instead of median, we used mean, which was easier to track for the large amounts of data.