Causal Effects of Genetically Predicted Cardiovascular Risk Factors on Chronic Kidney Disease: A Two-Sample Mendelian Randomization Study
In this study, we used cardiovascular risk factors as the exposures, including HDL cholesterol, LDL cholesterol, TC and TG for lipids, HbA1c and fasting glucose for glycemic traits, SBP and DBP for blood pressure, and CKD as the outcome to perform the TSMR analysis.
FIGURE 1
Figure 1. Schematic representation of TSMR analysis. Three assumptions of MR analysis are as follows: (1) IVs must be associated with cardiovascular risk factors, (2) IVs must not be associated with confounders, and (3) IVs must influence CKD only through cardiovascular risk factors. IVs, instrumental variables; HDL, high density lipoprotein; LDL, low density lipoprotein; TC, total cholesterol; TG, triglyceride; HbA1c, glycated hemoglobin; SBP, systolic blood pressure; DBP, diastolic blood pressure; CKD, chronic kidney disease.
IVs Selection and Validation
Instrumental variables must be associated with cardiovascular risk factors, including HDL cholesterol, LDL cholesterol, TC, TG, HbA1c, fasting glucose, SBP, and DBP. To ensure the close relationship between IVs and cardiovascular risk factors, we selected variants with P < 5 × 10−8 in the corresponding GWAS summary-level dataset. In addition, pairwise-linkage disequilibrium (LD) was calculated by PLINK 1.90 (Purcell et al., 2007) to ensure the independence among selected IVs and SNPs with r2> 0.001 will be removed from our analysis.
Selected IVs should be independent of any known confounders and conditionally inde...
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
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