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Association of genetic variants related to plasma fatty acids with type 2 diabetes mellitus and glycaemic traits: a Mendelian randomisation study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden.ORCID iD: 0000-0003-0118-0341
(English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428Article in journal (Refereed) Epub ahead of print
Abstract [en]

Aims/hypothesis: Epidemiological data on the associations of circulating fatty acid levels with type 2 diabetes are inconsistent. We conducted a two-sample Mendelian randomisation study to explore the causal associations of plasma levels of ten fatty acids with type 2 diabetes and glycaemic traits.

Methods: Thirteen SNPs associated with circulating levels of ten individual fatty acids at the genome-wide significance level (p < 5 x 10(-8)) were selected as instrumental variables for the exposures. For the outcomes, summary-level data were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for type 2 diabetes (898,130 individuals) and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the glycaemic traits (up to 46,186 non-diabetic individuals). The inverse-variance weighted method was used for analyses.

Results: Genetic predisposition to higher plasma levels of eight of the ten fatty acids were statistically significantly associated with lower or higher odds of type 2 diabetes. The OR per one SD increment of each fatty acid was 0.93 (95% CI 0.90, 0.96; p = 2.21 x 10(-5)) for alpha-linolenic acid, 0.96 (95% CI 0.94, 0.98; p = 1.85 x 10(-4)) for linoleic acid, 0.86 (95% CI 0.81, 0.91; p = 6.68 x 10(-7)) for palmitoleic acid, 0.87 (95% CI 0.81, 0.93; p = 2.21 x 10(-5)) for oleic acid, 1.08 (95% CI 1.03, 1.12; p = 0.002) for eicosapentaenoic acid, 1.04 (95% CI 1.02, 1.07; p = 0.001) for docosapentaenoic acid, 1.03 (95% CI 1.02, 1.05; p = 2.51 x 10(-5)) for arachidonic acid and 1.09 (95% CI 1.03, 1.15; p = 0.003) for stearic acid. The same eight fatty acids were also associated with fasting glucose levels and HOMA-B. The associations, except that for palmitoleic acid, were driven by variants in FADS1/2.

Conclusions/interpretation: Genetic predisposition to higher circulating levels of eight out of ten fatty acids was associated with type 2 diabetes, fasting glucose and islet beta cell function. However, the associations, except that for palmitoleic acid, were driven by variants in FADS1/2, which encode enzymes with a key role in fatty acid metabolism.

Place, publisher, year, edition, pages
SPRINGER.
Keywords [en]
Fatty acids, Genetic variants, Glycaemic traits, Mendelian randomisation, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:uu:diva-397603DOI: 10.1007/s00125-019-05019-0ISI: 000494514500003PubMedID: 31690987OAI: oai:DiVA.org:uu-397603DiVA, id: diva2:1372184
Funder
Swedish Research CouncilAvailable from: 2019-11-22 Created: 2019-11-22 Last updated: 2019-11-22

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