Expressive

rs10891647 (NNMT): Plasma Metabolite Variant

Key takeaways

  • rs10891647 sits near the NNMT gene, which encodes an enzyme called Nicotinamide N-methyltransferase
  • It was identified in one of the largest metabolomics genome-wide studies to date, covering 913 plasma metabolites in nearly 20,000 people
  • The study found 2,599 total variant-metabolite associations using a stringent significance cutoff (P < 1.25 x 10^-11)
  • Both rare and common genetic variants shape plasma metabolite levels, with rare variants accounting for 9.4% of all identified associations in this study

Key takeaways

  • rs10891647 sits near the NNMT (Nicotinamide N-methyltransferase) gene and C11orf71 on chromosome 11, a locus associated with differences in plasma metabolite levels
  • This variant was identified in one of the largest untargeted metabolomics genome-wide association studies to date, covering 913 metabolites in up to 19,994 individuals
  • The parent study found 2,599 total variant-metabolite associations at a stringent significance threshold (P < 1.25 x 10^-11) across 330 genomic regions
  • Both rare and common genetic variants shape plasma metabolite levels, with rare variants (minor allele frequency of 1% or less) accounting for 9.4% of all associations in the study

What the research says A genome-wide association meta-analysis examined 913 plasma metabolites in up to 19,994 individuals of European ancestry from the INTERVAL and EPIC-Norfolk cohorts, using an untargeted mass spectrometry platform (Metabolon HD4), and identified 2,599 conditionally independent variant-metabolite associations (P < 1.25 x 10^-11) within 330 genomic regions, with the NNMT-C11orf71 locus among those identified. The study grouped co-regulated variant-metabolite findings into 423 clusters called "genetically influenced metabotypes" - defined as sets of metabolites whose plasma levels are jointly regulated by variants in the same genomic region - and assigned causal genes for 62.4% of these clusters through literature-based curation. Rare variants contributed 9.4% of the 2,599 identified associations across the full study.

Reported associations

  • Plasma metabolite levels: rs10891647 is located in one of the 330 genomic regions identified as associated with plasma metabolite levels in this study of 913 metabolites in up to 19,994 individuals; the specific metabolites linked to this locus are reported in the study's supplementary data, which was not available in the text excerpt provided for this entry

Evidence quality The study providing context for this variant is a large-scale meta-analysis with a discovery sample of 14,296 individuals from INTERVAL and EPIC-Norfolk (European ancestry) and a validation sample of 5,698 additional EPIC-Norfolk participants, totaling up to 19,994 individuals across both stages. A rigorous significance threshold of P < 1.25 x 10^-11 was applied throughout. The untargeted Metabolon HD4 platform enabled broad coverage across 913 metabolites spanning lipids, amino acids, cofactors and vitamins, and other compound classes. However, per-locus data for rs10891647 - including the identities of associated metabolites, allele-specific effect sizes, and independent replication details for this specific locus - are not available in the study excerpt provided for this entry. The overall study design is well-powered and uses established methodology for metabolome-wide association analysis, but the variant-level evidence for rs10891647 cannot be fully evaluated from the text available here.

Lifestyle considerations No lifestyle considerations on file for this variant.

Frequently asked questions

What is rs10891647?

rs10891647 is a genetic variant located near the NNMT gene (Nicotinamide N-methyltransferase) and C11orf71 on chromosome 11. It was identified in a large genome-wide metabolomics study as one of thousands of variants associated with differences in plasma metabolite levels.

What is the NNMT gene?

NNMT stands for Nicotinamide N-methyltransferase, an enzyme whose name describes its role in methylating nicotinamide-related compounds. Variants near this gene have been linked to differences in plasma metabolite levels in large population-based genomic studies.

How was rs10891647 discovered?

It was identified in a genome-wide association meta-analysis of 913 plasma metabolites measured in up to 19,994 individuals of European ancestry from two cohort studies (INTERVAL and EPIC-Norfolk), using an untargeted mass spectrometry platform (Metabolon HD4) for broad metabolome coverage.

Is rs10891647 linked to any disease?

The study that identified this variant focused on plasma metabolite levels rather than disease outcomes. No disease associations for this specific variant are detailed in the study data available for this entry.

What is a genetically influenced metabotype?

A genetically influenced metabotype is a group of metabolites whose plasma levels are co-regulated by variants in the same genomic region. The study identified 423 such clusters across the human genome, representing coordinated genetic influences on sets of related metabolites.