Background
Methods
UCLEB
Metabolomics
Statistical analysis
Results
Basic characteristics of UCLEB participants
Trait | No-T2D participants | T2D participants | p value | ||
---|---|---|---|---|---|
n | Trait | n | Trait | ||
Age (years) | 13,015 | 61.1 (6.0) | 1803 | 61.3 (8.1) | 0.32 |
Sex (percentage male) | 8068 | 62.00 | 1053 | 58.4 % | 0.003 |
BMI (kg/m2)
| 12,803 | 26.7 (4.3) | 1747 | 28.6 (5.80) | 1.346 × 10−36
|
Triglycerides (mmol/l)a
| 12,022 | 0.43 (0.55) | 1563 | 0.67 (0.75) | 8.461 × 10−33
|
Total Cholesterol (mmol/l) | 12,736 | 6.28 (1.24) | 1784 | 6.04 (1.65) | 4.484 × 10−8
|
HDL-cholesterol (mmol/l) | 12,493 | 1.42 (0.38) | 1757 | 1.25 (0.51) | 2.114 × 10−34
|
LDL-cholesterol (mmol/l) | 12,385 | 4.00 (1.07) | 1607 | 3.62 (1.43) | 1.573 × 10−21
|
Systolic blood pressure (mmHg) | 12,739 | 139.90 (22.80) | 1783 | 148.00 (30.60) | 1.650 × 10−23
|
Diastolic blood pressure (mmHg) | 12,722 | 81.70 (12.90) | 1782 | 84.40 (17.30) | 3.716 × 10−9
|
Fasting glucose (mmol/l)a
| 12,741 | 1.69 (0.15) | 1670 | 1.98 (0.19) | 2.54 × 10−303
|
Insulin (µIU/ml)a
| 7732 | 1.89 (0.62) | 456 | 2.50 (0.66) | 1.686 × 10−80
|
Glycated haemoglobin (%) | 8711 | 5.37 (0.65) | 1807 | 6.80 (0.98) | 8.14 × 10−265
|
Rs10911021 and CHD in T2D
BRHS | BWHHS | CAPS | EAS | ELSA | ET2DS | MRC1946 | WHII | Combined | |
---|---|---|---|---|---|---|---|---|---|
No T2D | |||||||||
MAF no CHD | 0.30 (1544) | 0.32 (1528) | 0.31 (1022) | 0.31 (553) | 0.30 (1426) | – | 0.32 (2294) | 0.31 (2851) | 0.31 (8665) |
MAF CHD | 0.30 (378) | 0.31 (285) | 0.28 (239) | 0.29 (132) | 0.29 (114) | – | 0.31 (65) | 0.35 (161) | 0.30 (1677) |
OR (95 % CI) | 1.02 (0.85–1.22) | 1.01 (0.79–1.28) | 0.82 (0.65–1.04) | 0.90 (0.67–1.23) | 1.10 (0.81–1.49) | – | 1.00 (0.68–1.47) | 1.23 (0.97–1.56) | 1.00 (0.92–1.10) |
p value | 0.81 | 0.94 | 0.10 | 0.64 | 0.54 | – | 0.43 | 0.09 | 0.93 |
T2D | |||||||||
MAF no CHD | 0.31 (190) | 0.34 (94) | 0.30 (20) | 0.23 (46) | 0.32 (160) | 0.30 (793) | 0.28 (45) | 0.31 (29) | 0.30 (1377) |
MAF CHD | 0.18 (72) | 0.20 (13) | 0.29 (16) | 0.24 (13) | 0.29 (7) | 0.32 (31) | 0.40 (5) | 0.30 (3) | 0.26 (160) |
OR (95 % CI) | 0.44 (0.26–0.74) | 0.48 (0.17–1.33) | 1.43 (0.51–4.00) | 1.05 (0.36–3.03) | 0.85 (0.25–2.94) | 1.35 (0.80–2.33) | 1.69 (0.46–6.25) | 1.01 (0.52–1.96) | 0.80 (0.60–1.06) |
p value | 2 × 10−3
| 0.16 | 0.49 | 0.95 | 0.80 | 0.26 | 0.43 | 0.87 | 0.13 |
rs10911021 and the γ-glutamyl cycle in T2D
Trait (mmol/l) | Beta-coefficient (se) | p value |
---|---|---|
Alanine | −0.007 (0.07) | 0.94 |
Glutamine | 0.005 (0.08) | 0.94 |
Glycine | 0.003 (0.07) | 0.97 |
Histidine | 0.03 (0.07) | 0.66 |
Isoleucine | 0.02 (0.07) | 0.74 |
Leucine | −0.005 (0.07) | 0.94 |
Valine | 0.06 (0.07) | 0.44 |
Phenylalanine | 0.04 (0.07) | 0.58 |
Tyrosine | −0.03 (0.07) | 0.65 |
rs10911021 and conventional risk factors for CHD and T2D
Trait | Number of non-T2D participants | Beta-coefficient in non-T2D participants (se) | p value | Number of T2D participants | Beta- coefficient in T2D participants (se) | p value |
---|---|---|---|---|---|---|
BMI (kg/m2) | 12,803 | −0.032 (0.055) | 0.56 | 1747 | −0.055 (0.178) | 0.76 |
Triglycerides (mmol/l)a
| 12,022 | 0.007 (0.007) | 0.34 | 1563 | 0.030 (0.020) | 0.87 |
Total cholesterol (mmol/l) | 12,736 | −0.011 (0.016) | 0.25 | 1784 | 0.026 (0.043) | 0.54 |
HDL cholesterol (mmol/l) | 12,493 | −0.001 (0.005) | 0.86 | 1757 | −0.034 (0.012) | 0.0005 |
LDL cholesterol (mmol/l) | 12,385 | −0.018 (0.014) | 0.21 | 1607 | 0.070 (0.037) | 0.06 |
Systolic blood pressure (mmHg) | 12,739 | 0.045 (0.298) | 0.88 | 1783 | 0.056 (0.794) | 0.94 |
Diastolic blood pressure (mmHg) | 12,722 | 0.052 (0.170) | 0.76 | 1782 | −0.510 (0.432) | 0.24 |
Fasting glucose (mmol/l)a
| 12,740 | 0.001 (0.002) | 0.61 | 1670 | −0.011 (0.009) | 0.21 |
Insulin (µIU/ml)a
| 7732 | −0.019 (0.011) | 0.09 | 456 | 0.039 (0.063) | 0.53 |
Glycated haemoglobin (%) | 8711 | −0.003 (0.008) | 0.73 | 1317 | 0.032 (0.040) | 0.42 |
rs10911021 Genotype | p value | |||
---|---|---|---|---|
CC | CT | TT | ||
T2D participants | ||||
HDL-C (mmol/l) | 1.35 (0.35) | 1.31 (0.32) | 1.31 (0.33) | 0.0005 |
N | 859 | 740 | 158 | |
No T2D participants | ||||
HDL-C (mmol/l) | 1.14 (0.35) | 1.40 (0.36) | 1.31 (0.33) | 0.86 |
N | 5975 | 5400 | 1118 |
Trait (mol/l) | Number of non-T2D participants | Beta-effect in non-T2D participants (se) | p value | FDR adjusted p value | Heterogeneity [I2 (%)] | Number of T2D participants | Beta-effect in T2D participants (se) | p value | FDR adjusted p value | Heterogeneity [I2 (%)] | p value for conditional analysis with rs1689800 | FDR adjusted p value for conditional analysis with rs1689800 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
Concentration of large HDL particles | 5221 | 0.01 (0.02) | 0.59 | 1 | 0 | 1310 | −0.15 (0.04) | 0.0005 | 0.03 | 0 | 0.001 | 0.07 |
Total lipids in large HDL | 5229 | 0.01 (0.02) | 0.62 | 1 | 0 | 1310 | −0.15 (0.04) | 0.0005 | 0.03 | 0 | 0.001 | 0.07 |
Phospholipids in large HDL | 5223 | 0.01 (0.02) | 0.59 | 1 | 0 | 1310 | −0.14 (0.04) | 0.0009 | 0.03 | 0 | 0.002 | 0.09 |
Total cholesterol in large HDL | 5223 | 0.008 (0.02) | 0.71 | 1 | 0 | 1310 | −0.15 (0.04) | 0.0004 | 0.04 | 0 | 0.001 | 0.07 |
Cholesterol esters in large HDL | 5221 | 0.009 (0.02) | 0.67 | 1 | 0 | 1310 | −0.15 (0.04) | 0.0004 | 0.03 | 0 | 0.001 | 0.07 |
Free cholesterol in large HDL | 5221 | 0.005 (0.02) | 0.83 | 1 | 0 | 1310 | −0.16 (0.04) | 0.0003 | 0.03 | 0 | 0.0009 | 0.07 |
Trait (mol/l) | Beta-effect (se) | p value | FDR adjusted p value |
---|---|---|---|
Concentration of large HDL particles | 6.70 × 10−4 (0.01) | 0.95 | 1 |
Total lipids in large HDL | 5.28 × 10−4 (0.01) | 0.96 | 1 |
Phospholipids in large HDL | 4.38 × 10−3 (0.01) | 0.74 | 1 |
Total cholesterol in large HDL | 1.40 × 10−3 (0.01) | 0.85 | 1 |
Cholesterol esters in large HDL | 2.81 × 10−3 (0.01) | 0.75 | 1 |