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Ryan Longchamps, MSPhD candidate, Human Genetics Predoctoral Training Program, McKusick-Nathans Institute of Genetic Medicine
(B.S. Physiology and Neurobiology)
BWF PUP program: Johns Hopkins University Bloomberg School of Public Health "MD-GEM: The Maryland Genetic, Epidemiology, and Medicine Training Program"
Interests: The role of mitochondrial DNA (mtDNA) quantity, in the form mtDNA copy number (mtDNA CN), as well as mtDNA quality, in the form of mtDNA heteroplasmy, in the prevalence and incidence of coronary artery disease (CAD).
Current Projects: I am currently working on exploring the role of mitochondrial DNA (mtDNA) quantity, in the form mtDNA copy number (mtDNA CN), as well as mtDNA quality, in the form of mtDNA heteroplasmy, in the prevalence and incidence of coronary artery disease (CAD).
By optimizing methods for measuring mtDNA CN from microarray data we can employ a large genome wide association study (GWAS) from preexisting data within the CHARGE consortium. Through this GWAS we aim to find nuclear and mitochondrial variants which affect mtDNA CN. At its current stage, we have summary statistics from 41,908 individuals (18.2% Blacks, 1.8 % Chinese, 2.8% Hispanic) and expect data from an additional 52,310 individuals by September. Additionally, we have applications submitted to the UK Biobank to calculate mtDNA CN from the Affymetrix Axiom array for their ~500,000 samples. Future work will aim to employ Mendelian Randomization (MR) to explore causality of mtDNA CN with CAD.
In an interim meta-analysis in whites (n = 32,300) we identified one genome-wide significant loci (rs10432360), which lies downstream of ZEB2 which encodes a zinc finger protein responsible for transcriptional repression. Additionally, we observe an enrichment of loci with p-values < 5e10-7 (3 expected, 6 observed). No genomewide significant loci were discovered in our other ethnic groups, however this is most likely due to sample size. Interim MR analysis in whites reveals no significant causal relationship between mtDNA CN and CAD (beta = -0.016, p-value = 0.17), however the direction of effect suggests mtDNA CN may mitigate CAD risk. We anticipate the doubling of our sample size will identify several more genome-wide significant loci as well as further elucidate the causal relationship between mtDNA CN and CAD.
System of Study:
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