ArticleCirculation. Cardiovascular genetics2016
Interaction of Insulin Resistance and Related Genetic Variants With Triglyceride-Associated Genetic Variants.
Article in Circulation. Cardiovascular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- Heterogeneous effects of genetic variants and traits associated with fasting insulin on cardiometabolic outcomes.Nature communications · 2025Article
- Vitamin D is negatively associated with triglyceride in overweight/obese patients with type 2 diabetes.Endocrine · 2022Article
- Increasing fasting glucose and fasting insulin associated with elevated bone mineral density-evidence from cross-sectional and MR studies.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Article
- Postoperative serum triglyceride levels in predicting risk of new-onset diabetes mellitus in patients following liver transplantation.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2021Article
- Gene-environment interactions due to quantile-specific heritability of triglyceride and VLDL concentrations.Scientific reports · 2020Article
- Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study.Experimental gerontology · 2018Article
- Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years.Journal of lipid research · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSeveral studies suggest that some triglyceride-associated single-nucleotide polymorphisms (SNPs) have pleiotropic and opposite effects on glycemic traits. This potentially implicates them in pathways such as de novo lipogenesis, which is presumably upregulated in the context of insulin resistance. We therefore tested whether the association of triglyceride-associated SNPs with triglyceride levels differs according to one's level of insulin resistance. METHODS AND
resultsIn 3 cohort studies (combined n=12 487), we tested the interaction of established triglyceride-associated SNPs (individually and collectively) with several traits related to insulin resistance, on triglyceride levels. We also tested the interaction of triglyceride SNPs with fasting insulin-associated SNPs, individually and collectively, on triglyceride levels. We find significant interactions of a weighted genetic risk score for triglycerides with insulin resistance on triglyceride levels (Pinteraction=2.73×10(-11) and Pinteraction=2.48×10(-11) for fasting insulin and homeostasis model assessment of insulin resistance, respectively). The association of the triglyceride genetic risk score with triglyceride levels is >60% stronger among those in the highest tertile of homeostasis model assessment of insulin resistance compared with those in the lowest tertile. Individual SNPs contributing to this trend include those in/near GCKR, CILP2, and IRS1, whereas PIGV-NROB2 and LRPAP1 display an opposite trend of interaction. In the pooled data set, we also identify a SNP-by-SNP interaction involving a triglyceride-associated SNP, rs4722551 near MIR148A, with a fasting insulin-associated SNP, rs4865796 in ARL15 (Pinteraction=4.1×10(-5)).
conclusionsOur findings may thus provide genetic evidence for the upregulation of triglyceride levels in insulin-resistant individuals, in addition to identifying specific genetic loci and a SNP-by-SNP interaction implicated in this process.
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