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Association of gene...
Association of genetic variants related to plasma fatty acids with type 2 diabetes mellitus and glycaemic traits : a Mendelian randomisation study
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- Yuan, Shuai (författare)
- Karolinska Institutet,Uppsala universitet,Institutionen för kirurgiska vetenskaper,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden
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- Larsson, Susanna C. (författare)
- Karolinska Institutet,Uppsala universitet,Ortopedi,Karolinska Inst, Inst Environm Med, Unit Cardiovasc & Nutr Epidemiol, Nobelsvag 13, S-17177 Stockholm, Sweden
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(creator_code:org_t)
- 2019-11-05
- 2020
- Engelska.
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Ingår i: Diabetologia. - : Springer Nature. - 0012-186X .- 1432-0428. ; 63:1, s. 116-123
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Fatty acids
- Genetic variants
- Glycaemic traits
- Mendelian randomisation
- Type 2 diabetes
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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