Excited to say that the mitochondrial DNA copy number GWAS that I worked on with @RyanLongchamps in @dan_arking's lab is now up on BioRxiv! https://www.biorxiv.org/content/10.1101/2021.01.25.428086v1

In this work, we use data from the CHARGE cohorts and the #UKBiobank to perform a genome-wide association study for mitochondrial DNA copy number (mtDNA-CN) in over 400,000 individuals. We identify 129 independent signals that pass genome-wide significance (GWS).

Through a combination of fine-mapping, variant annotation, and colocalization analyses, we prioritize genes for each locus. These identified genes are significantly enriched for genes that are known to cause mtDNA depletion syndromes.

Next, we use PHESANT to evaluate associations between mtDNA-CN GWS SNPs and other phenotypes. Since SNPs can presumably modify mtDNA-CN through different functional pathways, we then clustered SNPs by phenotypic effect size estimates.

Through this clustering approach, we find five distinct groups of SNPs. Genes within the different clusters are suggestive of processes that may directly modify or reflect changes in mtDNA-CN, including platelet activation, megakaryocyte proliferation, and mtDNA metabolism.