Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis
Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however,...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Karger Publishers
2020-08-01
|
| Series: | Lifestyle Genomics |
| Subjects: | |
| Online Access: | https://www.karger.com/Article/FullText/509663 |
| _version_ | 1818157184422248448 |
|---|---|
| author | Michael A. Zulyniak Harriett Fuller Mark M. Iles |
| author_facet | Michael A. Zulyniak Harriett Fuller Mark M. Iles |
| author_sort | Michael A. Zulyniak |
| collection | DOAJ |
| description | Background: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants’ siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10–8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (–0.038 ± 0.012 mM–1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR <1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk. |
| first_indexed | 2024-12-11T15:10:09Z |
| format | Article |
| id | doaj.art-67d2fe3d69c44ab0855b31dd28bc2230 |
| institution | Directory Open Access Journal |
| issn | 2504-3161 2504-3188 |
| language | English |
| last_indexed | 2024-12-11T15:10:09Z |
| publishDate | 2020-08-01 |
| publisher | Karger Publishers |
| record_format | Article |
| series | Lifestyle Genomics |
| spelling | doaj.art-67d2fe3d69c44ab0855b31dd28bc22302022-12-22T01:00:46ZengKarger PublishersLifestyle Genomics2504-31612504-31882020-08-011810.1159/000509663509663Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization AnalysisMichael A. ZulyniakHarriett FullerMark M. IlesBackground: Globally, 1 in 11 adults has diabetes mellitus, and most of these cases are type 2 diabetes (T2D). The risk of T2D is influenced by many factors, including diet. The synthesis of long-chain n-6 polyunsaturated fatty acids (LC n-6 PUFA) has been posited as a risk factor for T2D; however, its causal role is uncertain. Aim: To test the causal effect of LC n-6 PUFA synthesis on insulin resistance and transgenerational T2D risk in a large cohort of men and women. Methods: Two-sample mendelian randomization (MR) was conducted to evaluate the effect of low or high levels of LC n-6 PUFA synthesis on glycemia and development of T2D in the UK Biobank (n = 463,010) and Meta-Analysis of Glucose- and Insulin-Related Traits Consortium (MAGIC; n = 5,130) cohorts. The increased likelihood of a predisposition to low or high LC n-6 PUFA synthesis and the risk of T2D was also investigated using the participants’ siblings and parents. In MR-Base, 4 genetic variants associated with LC n-6 PUFA synthesis were found (p < 10–8). After pruning, 1 variant (rs174547) on the FADS1 gene was retained. Results: Lower LC n-6 PUFA synthesis and abundance (per % unit decrease) are associated with small reductions in the insulin disposition index (–0.038 ± 0.012 mM–1; p = 0.002) within MAGIC. In the UK Biobank, we report negligible effects of low n-6 PUFA synthesis on the odds of T2D (OR <1%; p < 0.05). Additionally, reduced LC n-6 PUFA synthesis does not appear to be a contributor to familial T2D risk. No significant association was observed between LC n-6 PUFA synthesis and BMI. Conclusion: In a primarily white European population, LC n-6 PUFA synthesis is not a major contributor to T2D risk.https://www.karger.com/Article/FullText/509663mendelian randomizationpolyunsaturated fatty acidomegafadsglycemiamagicuk biobankchargegiant |
| spellingShingle | Michael A. Zulyniak Harriett Fuller Mark M. Iles Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis Lifestyle Genomics mendelian randomization polyunsaturated fatty acid omega fads glycemia magic uk biobank charge giant |
| title | Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis |
| title_full | Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis |
| title_fullStr | Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis |
| title_full_unstemmed | Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis |
| title_short | Investigation of the Causal Association between Long-Chain n-6 Polyunsaturated Fatty Acid Synthesis and the Risk of Type 2 Diabetes: A Mendelian Randomization Analysis |
| title_sort | investigation of the causal association between long chain n 6 polyunsaturated fatty acid synthesis and the risk of type 2 diabetes a mendelian randomization analysis |
| topic | mendelian randomization polyunsaturated fatty acid omega fads glycemia magic uk biobank charge giant |
| url | https://www.karger.com/Article/FullText/509663 |
| work_keys_str_mv | AT michaelazulyniak investigationofthecausalassociationbetweenlongchainn6polyunsaturatedfattyacidsynthesisandtheriskoftype2diabetesamendelianrandomizationanalysis AT harriettfuller investigationofthecausalassociationbetweenlongchainn6polyunsaturatedfattyacidsynthesisandtheriskoftype2diabetesamendelianrandomizationanalysis AT markmiles investigationofthecausalassociationbetweenlongchainn6polyunsaturatedfattyacidsynthesisandtheriskoftype2diabetesamendelianrandomizationanalysis |