TY - JOUR
T1 - Causal relationships between lipid and glycemic levels in an Indian population
T2 - A bidirectional Mendelian randomization approach
AU - Agarwal, Tripti
AU - Lyngdoh, Tanica
AU - Dudbridge, Frank
AU - Chandak, Giriraj Ratan
AU - Kinra, Sanjay
AU - Prabhakaran, Dorairaj
AU - Reddy, K Srinath
AU - Relton, Caroline L
AU - Davey Smith, George
AU - Ebrahim, Shah
AU - Gupta, Vipin
AU - Walia, Gagandeep Kaur
PY - 2020/1/29
Y1 - 2020/1/29
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0228269
DO - 10.1371/journal.pone.0228269
M3 - Article (Academic Journal)
C2 - 31995593
VL - 15
SP - e0228269
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
ER -