Abstract | BACKGROUND:
Dyslipidemia and abnormal glycemic traits are leading causes of morbidity and mortality. Although the association between the two traits is well established, there still exists a gap in the evidence for the direction of causality. OBJECTIVE: This study aimed to examine the direction of the causal relationship between lipids and glycemic traits in an Indian population using bidirectional Mendelian randomization (BMR). METHODS: The BMR analysis was conducted on 4900 individuals (2450 sib-pairs) from the Indian Migration Study. Instrument variables were generated for each lipid and glycemic trait (fasting insulin, fasting glucose, HOMA-IR, HOMA-β, LDL-cholesterol, HDL-cholesterol, total cholesterol and triglycerides) to examine the causal relationship by applying two-stage least squares (2SLS) regression in both directions. RESULTS:
Lipid and glycemic traits were found to be associated observationally, however, results from 2SLS showed that only triglycerides, defined by weighted genetic risk score (wGRS) of 3 SNPs (rs662799 at APOAV, rs780094 at GCKR and rs4420638 at APOE/C1/C4), were observed to be causally effecting 1.15% variation in HOMA-IR (SE = 0.22, P = 0.010), 1.53% in HOMA- β (SE = 0.21, P = 0.001) and 1.18% in fasting insulin (SE = 0.23, P = 0.009). No evidence for a causal effect was observed in the reverse direction or between any other lipid and glycemic traits. CONCLUSION: The study findings suggest that triglycerides may causally impact various glycemic traits. However, the findings need to be replicated in larger studies.
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Authors | Tripti Agarwal, Tanica Lyngdoh, Frank Dudbridge, Giriraj Ratan Chandak, Sanjay Kinra, Dorairaj Prabhakaran, K Srinath Reddy, Caroline L Relton, George Davey Smith, Shah Ebrahim, Vipin Gupta, Gagandeep Kaur Walia |
Journal | PloS one
(PLoS One)
Vol. 15
Issue 1
Pg. e0228269
( 2020)
ISSN: 1932-6203 [Electronic] United States |
PMID | 31995593
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Blood Glucose
- Cholesterol, HDL
- Cholesterol, LDL
- Insulin
- Lipids
- Triglycerides
- Cholesterol
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Topics |
- Adult
- Blood Glucose
(analysis)
- Cholesterol
(blood)
- Cholesterol, HDL
(blood)
- Cholesterol, LDL
(blood)
- Cross-Sectional Studies
- Female
- Genotyping Techniques
- Humans
- India
- Insulin
(blood)
- Insulin Resistance
(genetics)
- Least-Squares Analysis
- Lipids
(blood)
- Male
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Quantitative Trait, Heritable
- Triglycerides
(blood)
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