rs11665690 (DUS3L-NRTN): Mitochondrial DNA Traits
Key takeaways
- rs11665690, near DUS3L and NRTN, was identified in a 274,832-person genome-wide study of nuclear control over mitochondrial DNA behavior.
- The study found 92 nuclear loci tied to mitochondrial DNA copy number and 42 linked to maternally inherited heteroplasmy levels.
- Mitochondrial DNA copy number in blood declines linearly with age, and nuclear genetic variants may influence that decline.
- Specific effect sizes for rs11665690 are not reported, so the magnitude of its individual influence remains unclear.
Key takeaways
- rs11665690, near the DUS3L and NRTN genes, was identified in a 274,832-person genome-wide study of nuclear control over mitochondrial DNA behavior.
- The study found 92 nuclear loci tied to mitochondrial DNA copy number and 42 linked to maternally inherited heteroplasmy levels.
- Mitochondrial DNA copy number in blood declines linearly with age, and nuclear genetic variants may influence that decline.
- Specific effect sizes for rs11665690 are not reported in the available study text, so the magnitude of its individual influence remains unclear.
What the research says A genome-wide association study (GWAS) of 274,832 individuals used whole-genome sequencing to examine how nuclear DNA variants relate to two mitochondrial DNA (mtDNA) traits: copy number (the quantity of mtDNA per cell, abbreviated mtCN) and heteroplasmy (the coexistence of different mtDNA versions within one person). The analysis identified 92 nuclear loci associated with mtCN and 42 loci associated with levels of maternally inherited heteroplasmic insertions and deletions; the DUS3L-NRTN locus, where rs11665690 resides, falls among the nuclear regions implicated by this analysis. Following correction for blood cell composition, the study found that mtCN in blood declines linearly with age across the study population.
Reported associations
- Mitochondrial DNA copy number: A GWAS in 274,832 individuals spanning six ancestry groups identified 92 nuclear loci associated with mtCN in blood; this locus is among the nuclear regions identified in this study. Specific per-variant effect sizes are not detailed in the available study text.
- Mitochondrial DNA heteroplasmy (insertions and deletions): The same study identified 42 nuclear loci influencing the relative levels of maternally inherited heteroplasmic insertions and deletions. Whether this locus was identified for heteroplasmy, mtCN, or both traits is not specified in the available text.
Evidence quality The underlying study drew on whole-genome sequencing from 274,832 participants across six ancestry groups in the UK Biobank and All of Us programs, providing strong statistical power for the nuclear-mtDNA architecture findings. The study applied blood cell composition correction, an important methodological step that reduces confounding in mtCN measurements from blood. However, per-variant statistics for rs11665690 specifically, including p-value, effect direction, and effect size, are not detailed in the provided study text, and replication of this specific locus in independent cohorts is not described. The evidence for the broader nuclear control of mtDNA traits is well-powered, but variant-level conclusions here remain limited.
Lifestyle considerations No lifestyle considerations on file for this variant.
Frequently asked questions
What is rs11665690 associated with?
rs11665690 is a nuclear DNA variant near the DUS3L and NRTN genes identified in a large genome-wide study linking nuclear variants to mitochondrial DNA traits, including copy number and heteroplasmy, in 274,832 people.
What is mitochondrial DNA copy number?
Mitochondrial DNA copy number is the quantity of mitochondrial DNA molecules found in a cell. It varies by cell type, declines with age in blood, and can be influenced by variants in the nuclear genome.
What is heteroplasmy?
Heteroplasmy is the coexistence of more than one version of mitochondrial DNA within a single person. It can arise from inherited variation or from mutations accumulating over a lifetime, and nuclear genetic variants can influence the relative balance of those versions.
How large was the study that identified rs11665690?
The study included 274,832 individuals from the UK Biobank and All of Us research programs, spanning six ancestry groups, and used whole-genome sequencing data to identify nuclear loci linked to mitochondrial DNA traits.
What genes are near rs11665690?
rs11665690 is located near DUS3L and NRTN on the nuclear genome. The study identified this region as a nuclear locus associated with mitochondrial DNA traits but did not describe the specific biological roles of these neighboring genes in the available text.