rs10774335 (NTF3): Plasma Metabolite GWAS Variant

Key takeaways

• rs10774335 sits near the NTF3 gene and was identified in a plasma metabolite genome-wide association study.
• The study analyzed 217 plasma metabolites in 2,076 Framingham Heart Study participants and found 31 associated genetic loci, including 23 that had not been previously reported.
• For most metabolites examined, inherited factors explained more inter-individual variation than measured clinical factors such as age, sex, body mass index, and blood pressure.
• The specific metabolite linked to this variant is not detailed in the available study excerpt.
• Evidence is from a single cohort with no reported independent replication, and should be considered preliminary.

What the research says A genome-wide association study (GWAS) of 217 plasma metabolites - including more than 100 not measured in prior GWAS - was conducted in 2,076 participants of the Framingham Heart Study Offspring Cohort, identifying 31 genetic loci associated with circulating metabolite levels, 23 of which had not been previously reported; rs10774335, near the NTF3 locus, is reported in the context of this study. For 66% of metabolites, estimated heritability (the proportion of inter-individual variation attributable to inherited factors) exceeded 20%, while for 93% of metabolites, measured clinical factors accounted for 20% or less of inter-individual variation. Non-essential amino acids showed the highest average heritability (mean h2 = 0.53, range 0.15 to 0.82), compared with essential amino acids (mean h2 = 0.29, range 0.14 to 0.43), a difference that was statistically significant (P = 0.01).

Reported associations

• Plasma metabolite levels: rs10774335, near the NTF3 locus, was identified among 31 genetic loci associated with circulating plasma metabolite concentrations in a community-based cohort of 2,076 Framingham Heart Study participants; the specific metabolite(s) associated with this locus are not named in the available study excerpt.

Evidence quality The available evidence comes from a single community-based cohort, the Framingham Heart Study Offspring Cohort (n = 2,076). The parent GWAS identified 31 loci with genome-wide significant associations across 217 metabolites, including 23 that were novel at the time of publication. A sample size of 2,076 is modest by current GWAS standards for metabolite traits. Independent replication of the specific rs10774335 association in external cohorts is not described in the provided study excerpt. Because only one study is available and specific effect size data for this locus are not detailed in the available text, the evidence should be treated as preliminary.

Lifestyle considerations No lifestyle considerations on file for this variant.