Table 1. Association with “gold-standard” insulin resistance measures, type 2 diabetes and coronary heart disease of genetic scores comprising lead polymorphisms at identified loci.
Results are displayed for genetic scores comprising either (a) the lead SNP at each of the 53 associated loci or (b) the lead SNP at each of the 43 additional loci identified in this study after removing 10 previously implicated in insulin resistance or (c) the lead SNP at each of the 28 loci not previously associated with levels of HDL cholesterol or triglycerides.
| Exposure | Outcome | Sample size, N or N cases and N controls | Beta or odds ratio | SE or 95% CI | p-value |
|---|---|---|---|---|---|
| Association with “gold-standard” measures of insulin sensitivity | |||||
| 53-SNP score | Insulin sensitivitya | 2,764 | -0.09 | 0.019 | 4.3 x 10-06 |
| 43-SNP score | -0.08 | 0.022 | 4.6 x 10-04 | ||
| 28-SNP score | -0.09 | 0.022 | 2.6 x 10-05 | ||
| 53-SNP score | Insulin sensitivity indexb | 4,769 | -0.10 | 0.016 | 7.3 x 10-10 |
| 43-SNP score | -0.08 | 0.018 | 4.6 x 10-05 | ||
| 28-SNP score | -0.09 | 0.027 | 0.0010 | ||
| Association with disease endpoints | |||||
| 53-SNP score | Type 2 diabetes | 45,836 cases and 230,358 controls | 1.12 | 1.11, 1.14 | 9.2 x 10-61 |
| 43-SNP score | 1.09 | 1.08, 1.11 | 7.6 x 10-29 | ||
| 28-SNP score | 1.11 | 1.09, 1.13 | 1.9 x 10-25 | ||
| 53-SNP score | Coronary heart disease | 63,746 cases and 130,681 controls | 1.05 | 1.04, 1.06 | 1.8 x 10-13 |
| 43-SNP score | 1.04 | 1.03, 1.06 | 5.7 x 10-08 | ||
| 28-SNP score | 1.04 | 1.02, 1.06 | 1.2 x 10-05 | ||
Abbreviations: N, number of participants; SE, standard error; CI, confidence interval; SNP, single nucleotide polymorphism. Beta coefficients are in standardised units per standard deviation of the 53-SNP genetic score (i.e. 4.5 alleles); odds ratios are per standard deviation of the 53-SNP genetic score (i.e. 4.5 alleles). The association with insulin sensitivity is from 2,764 participants of the GENESIS consortium27 and the association with the insulin sensitivity index is from 4,769 participants of the MAGIC consortium who underwent a frequently sampled oral glucose tolerance test (OGTT)33; the association with type 2 diabetes is from the InterAct, DIAGRAM and UK Biobank studies; the association with coronary heart disease is from the CARDIoGRAM and the C4D consortia.
In MAGIC, insulin sensitivity index (ISI) = 10,000/√ (fasting plasma glucose (mg/dl)×fasting insulin×mean glucose during OGTT (mg/dl)×mean insulin during OGTT).33
In GENESIS, insulin sensitivity was measured by clamp or insulin suppression test using study-specific parameters (e.g. glucose disposal or M-value) which were then standardised before meta-analysis.27