Background
Methods
EPIC-NL: Study design
Baseline measurements
Biomarker measurements
Genotyping
Gene | SNP (literature) | SNP (dataset) | MAF (dataset) | ref | r2SNPs |
---|---|---|---|---|---|
Insulin resistance
| |||||
PPARG
| rs1801282 | rs1801282 | G: 0.13 | [14] | - |
IRS1
| rs2943634 | rs2943634 | A: 0.35 | [15] | - |
GCKR
| rs780094 | rs780094 | T: 0.37 | [14] | - |
IGF1
| rs35767 | rs35767 | A: 0.16 | [14] | - |
GCK
| rs4607517 | rs1799884 | T: 0.18 | [14] | 1 |
Abdominal obesity
| |||||
FTO
| rs1421085 | rs1421085 | C: 0.40 | [16] | - |
MC4R
1
| rs17782313 | rs17782313 | C: 0.25 | [16] | - |
Inflammation
| |||||
IL6R
| rs4537545 | rs4537545 | T: 0.39 | [17] | - |
LEPR
| rs6700896 | rs1805096 | A: 0.38 | [17] | 0.89 |
CRP
| rs7553007 | rs1341665 | A: 0.32 | [17] | 1 |
ADIPOQ
| rs1648707 | rs182052 | A: 0.34 | [18] | 1 |
IL18
| rs1834481 | rs5744256 | G: 0.26 | [19] | 1 |
GCKR
| rs780094 | rs780094 | T: 0.37 | [20] | - |
Triglycerides
| |||||
AFF1
| rs442177 | rs3775214 | G: 0.43 | [21] | 0.96 |
APOB
| rs673548 | rs673548 | A: 0.22 | [22] | - |
APOB
| rs693 | rs693 | G: 0.50 | [23] | - |
APOA5-A4-C3-A1
| rs12286037 | rs12286037 | T: 0.08 | [24] | - |
APOA5
| rs6589566 | rs2075290 | C: 0.06 | [25] | 1 |
FADS1
| rs174548 | rs174548 | G: 0.29 | [21] | |
FADS1-2-3
| rs174547 | rs174577 | A: 0.35 | [26] | 1 |
GALNT2
| rs4846914 | rs4846914 | G: 0.41 | [23] | - |
LPL
| rs328 | rs328 | G: 0.10 | [23] | - |
MLXIPL
| rs17145738 | rs17145750 | T: 0.16 | [24] | 0.86 |
PLTP
| rs7679 | rs6073952 | A: 0.20 | [26] | 0.82 |
TRIB1
| rs2954029 | rs2954029 | T: 0.47 | [26] | - |
CLIP2
| rs16996148 | rs16996148 | T: 0.10 | [24] | - |
GCKR
| rs780094 | rs780094 | T: 0.37 | [27] | - |
ANGPTL3-DOCK7
| rs1748195 | rs1748197 | A: 0.35 | [24] | 1 |
ANGPTL3-DOCK7
| rs12130333 | rs12130333 | T: 0.24 | [23] | - |
HDL cholesterol
| |||||
ABCA1
| rs1883025 | rs1883025 | T: 0.24 | [26] | - |
ABCA1
| rs3890182 | rs3890182 | A: 0.10 | [21] | - |
APOB
| rs11902417 | rs11902417 | A: 0.24 | [21] | - |
CETP
| rs1800775 | rs1800775 | A: 0.46 | [28] | - |
CETP
| rs3764261 | rs3764261 | A: 0.31 | [29] | - |
FADS1
| rs174548 | rs174548 | G: 0.29 | [21] | - |
FADS1-2-3
| rs174547 | rs174577 | A: 0.35 | [26] | - |
GALNT2
| rs4846914 | rs4846914 | G: 0.41 | [23] | - |
LCAT
| rs255052 | rs255052 | A: 0.17 | [24] | - |
LCAT
| rs12449157 | rs1109166 | C: 0.18 | [21] | 0.94 |
LIPC
| rs1800588 | rs1800588 | T: 0.22 | [23] | - |
LIPG
| rs2156552 | rs2156552 | A: 0.16 | [21] | - |
LPL
| rs328 | rs328 | G: 0.10 | [23] | - |
PLTP
| rs7679 | rs6073952 | A: 0.20 | [26] | 0.82 |
MMAB MVK
| rs2338104 | rs10774708 | A: 0.47 | [26] | 1 |
HNF4A
| rs1800961 | rs1800961 | T: 0.04 | [26] | - |
Statistics
Results
Total (n=1886) | Men (n=465) | Women (n=1421) | |
---|---|---|---|
Sex (% men) | 24.6 (465) | ||
Age (yr) | 50.1 (11.7) | 43.9 (11.1) | 52.2 (11.2) |
Waist circumference (cm) | 85.5 (11.6) | 92.0 (11.4) | 82.9 (10.5) |
Abdominal obesity(%)a | 27.7(522) | 21.9 (102) | 29.6 (420) |
HbA1C (%) | 5.46 (0.69) | 5.27 (0.61) | 5.53 (0.71) |
Hyperglycemiaa | 28.3 (534) | 17.8 (83) | 31.7 (451) |
Diabetic medication(%) | 1.2 (22) | 0.2 (1) | 1.5 (21) |
HDL-cholesterol (mmol/L) | 1.27 (0.35) | 1.14 (0.28) | 1.31 (0.36) |
Low HDL-cholesterol(%)a | 47.8 (902) | 29.2 (136) | 53.9 (766) |
Triglyceride (mmol/L) b, c | 1.32 (0.91-1.98) | 1.72 (1.15-2.40) | 1.22 (0.85-1.80) |
Hypertriglyceridemia a, b | 33.8 (637) | 50.8 (236) | 28.2 (401) |
Systolic blood pressure (mm Hg) | 126.9 (18.5) | 127.1 (14.8) | 126.8 (19.5) |
Diastolic blood pressure (mm Hg) | 78.2 (10.4) | 80.3 (10.1) | 77.5 (10.4) |
Hypertension(%)a | 45.6 (860) | 47.1(219) | 45.1 (641) |
Blood pressure lowering medication (%) | 10.7 (202) | 5.6 (26) | 12.4 (176) |
High sensitive CRP (mmol/L) | 1.41 (0.62-3.39) | 1.20 (0.53-2.82) | 1.49 (0.66-3.70) |
MetS-score (number of features) | 1.8 (1.4) | 1.7 (1.3) | 1.9 (1.4) |
MetS prevalence(%)a | 30.3 (572) | 25.2 (117) | 32.0 (455) |
Group of SNPs | MetS | MetS-score | WC (cm) | HbA1C (%) | Log (TG) (mmol/L) | HDL (mmol/L) | SBP (mm HG) | DBP (mm HG) | Log (CRP) (mmol/L) |
---|---|---|---|---|---|---|---|---|---|
n
|
1886
|
1886
|
1886
|
1864
1
|
1886
|
1886
|
1684
3
|
1684
3
|
1683
2
|
WC
4
|
P=0.03
| P=0.08 |
P=0.01
| P=0.73 | P=0.81 | P=0.36 | P=0.29 | P=0.11 | P=0.22 |
Adj WC
| P=0.16 | P=0.80 | - | P=0.47 | P=0.55 | P=0.09 | P=0.36 | P=0.34 | P=0.68 |
IR
| P=0.06 |
P=0.003
| P=0.45 |
P=0.04
|
P=0.0003
|
P=0.0005
| P=0.07 | P=0.16 | P=0.16 |
Adj HbA1C
| P=0.12 |
P=0.01
| P=0.70 | - |
P=0.0005
|
P=0.0008
| P=0.10 | P=0.22 | P=0.17 |
MetS | MetS-score | |
---|---|---|
n
| 1886 | 1886 |
WC
| ||
FTO rs1421085 | 1.02(0.93; 1.12) | 0.05(−0.03; 0.14) |
MC4Rrs17782313 1 |
1.16(1.02; 1.32)
| 0.10(−0.05; 0.24) |
IR
| ||
PPARG rs1801282 | 1.04(0.91; 1.19) | 0.10(−0.02; 023) |
IRS1 rs2943634 |
0.88(0.79; 0.97)
|
−0.14(−0.23;-0.06)
|
GCKR rs780094 | 0.99(0.89; 1.09) | 0.05(−0.04; 0.13) |
IGF1 rs35767 | 1.03(0.91; 1.16) | 0.03(−0.08; 0.14) |
GCK rs1799884 | 1.07(0.95; 1.20) | 0.08(−0.03; 0.22) |