Table 1. The association of systemic lipids-related genotypes with risk of insulin resistance or T2DM.
| Instrumental variables | Genes or related traits | Study subjects | Outcomes | OR (95% CI) or the effect per SD change (β or z score) | p-value | References | |
|---|---|---|---|---|---|---|---|
| LDL-C | |||||||
| rs10455872 | LPA/↑Lipoprotein(a) | EPIC-Norfolk cohort (n=15,044) | T2DM | OR, 1.03; 95% CI, 0.96–1.10 | 0.41 | Ye et al.17 | |
| DIAGRAM consortium (n=63,390) | |||||||
| Genetic risk score from 26 SNPs | ↑Lipoprotein(a) | DIAGRAM consortium (n=149,821) | T2DM | β=−0.21 (−0.29, −0.12) | 5.0×10−6 | Fall et al.37 | |
| MAGIC (n=42,854) | Fasting insulin | β=−0.01 (−0.03, 0.00) | 0.13 | ||||
| Fasting glucose | β=−0.02 (−0.04, −0.01) | 5.6×10−3 | |||||
| rs10455872 | LPA/↑Lipoprotein(a) | Berlin Aging Study (n=2,012) | Fasting insulin | β=0.026 (−0.02, 0.07) | 0.285 | Buchmann et al.20 | |
| LIFE-Adult (n=3,281) and LIFE-Heart (n=2,816) | |||||||
| rs17238484 | ↑HMGCR/Statin treatment | Whitehall II study (n=4,678) | T2DM | β=1.12 (1.06, 1.18) | 0.253 | Swerdlow et al.21 | |
| Meta-analysis from 43 studies (n=223,463) | |||||||
| Triglyceride | |||||||
| Weighted score from rs2954029, rs714052, rs7557067, rs17216525, rs10889353, rs7679, rs7819412, rs328, rs3135506, rs662799 | TRIBI, MLXIPL, APOB, NCAN, CLIP2, PBX4, ANGPTL3, PLTP, XKR6-AMAC1L2, LPL, APOA5/↑Circulating triglycerides | Go-DARTs study (n=12,497) | Fasting insulin or Fasting glucose | z=0.04 (−0.03, 0.11) | 0.31 | De Silva et al.28 | |
| z=0.01 (−0.06, 0.08) | 0.74 | ||||||
| Genetic risk score from 23 SNPs | ↑Circulating triglycerides | DIAGRAM consortium (n=149,821) | T2DM | β=0.13 (0.01, 0.25) | 0.04 | Fall et al.37 | |
| MAGIC (n=42,854) | Fasting insulin | β=0.03 (0.00, 0.05) | 0.03 | ||||
| Fasting glucose | β=0.02 (0.00, 0.04) | 0.04 | |||||
| HDL-C | |||||||
| Genotype score from rs2575876, rs6494005, and rs3764261 | ABCA1, LIPC, and CETP/↑High-density lipoprotein | Nagahama Prospective Cohort for Comprehensive Human Bioscience (n=8,365) | HOMA-IR | Decreased HOMA-IR by quintile of HDL-C | 0.056 | Tabara et al.35 | |
| Genetic risk score from 5 SNPs | ↑High-density lipoprotein | DIAGRAM consortium (n=149,821) | T2DM | β=−0.12 (−0.24, −0.01) | 0.03 | Fall et al.37 | |
| MAGIC (n=42,854) | Fasting insulin | β=−0.01 (−0.03, 0.01) | 0.25 | ||||
| Fasting glucose | β=−0.01 (−0.05, −0.01) | 3.4×10−3 | |||||
| HDL-C lowering allele score from rs146292819, rs1800775, rs708272, rs4986970, rs1800588, rs199759119, and rs138407155 | ABCA1, CETP, LCAT, LIPC, and APOA1/↓High-density lipoprotein | CCHS, CGPS (n=47,627) | No association with T2DM | β=0.93 (0.78, 1.11) | 0.42 | Haase et al.34 | |
T2DM, type 2 diabetes mellitus; OR, odds ratio; CI, confidence interval; SD, standard deviation; LDL-C, low-density lipoprotein cholesterol; EPIC, European Prospective Investigation of Cancer; DIAGRAM, Diabetes Genetics Replication and Meta-analysis; SNP, single nucleotide polymorphism; MAGIC, Meta Analyses of Glucose and Insulin-related Traits Consortium; LIFE, Leipzig Research Centre for Civilization Diseases; HDL-C, high-density lipoprotein cholesterol; HOMA-IR, homeostatic model assessment for insulin resistance.