Online Supplementary Table 1 Clinical characteristics of the participants stratified with non-obese and
obese
characteristic
Non-obese
obese
p
girls/boys(n/n)
1 279/995
443/786
<0.001
12.7±3.1
11.8±2.9
<0.001
body mass index (kg/m )
19.40±3.53
26.54±3.67
<0.001
Fasting glucose(mg/dl)
91.13±12.20
92.81±8.68
<0.001
TG(mg/dl)
71.77(54.93-97.46)
93.92(70.44-127.58)
<0.001
TC(mg/dl)
158.57±33.54
158.18±28.70
0.73
HDL-C(mg/dl)
57.07±12.64
49.13±10.03
<0.001
LDL-C(mg/dl)
96.98±30.92
101.67±25.59
<0.001
age(years)
2
Abbreviations: BMI: body mass index; TG: triglycerides; TC: total cholesterol; HDL-C: high density
lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.
Data are shown as means+SD (for TC, HDL-C, and LDL-C) and as medians (25%-75% range) (for
TG).
Online Supplementary Table 2 Clinical characteristics of dyslipidemia and nondyslipidemia
characteristic
non-dyslipidemia
dyslipidemia
p
girls/boys(n/n)
1 256/1 248
464/526
0.08
age(years)
12.2±3.1
12.8±3.0
<0.001
body mass index (kg/m )
21.19±4.67
23.71±5.16
<0.001
Fasting glucose(mg/dl)
91.14±9.21
93.17±14.83
<0.001
TG(mg/dl)
70.88(54.27-92.14)
114.29(81.51-164.80)
<0.001
TC(mg/dl)
151.25±21.44
176.54±44.46
<0.001
HDL-C(mg/dl)
56.75±10.48
48.03±14.47
<0.001
LDL-C(mg/dl)
90.54±19.25
119.12±38.69
<0.001
2
Abbreviations: BMI: body mass index; TG: triglycerides; TC: total cholesterol; HDL-C: high density
lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.
Data are shown as means+SD (for TC, HDL-C, and LDL-C) and as medians (25%-75% range) (for
TG).
Online Supplementary Table 3 Genotypes distribution and Hardy-Weinberg equilibrium test for seven SNPs
genotypes
SNP
gene
chr.
Major /minor allele
group
C/C
C/R
R/R
MAF (%)
H-W-P
rs2144300
GALNT2
1
C/T
All
2 403
983
117
17
0.18
Boys
1 201
515
65
18
0.29
girls
1 202
468
52
17
0.43
All
1 063
1 694
746
45
0.14
Boys
533
864
384
46
0.33
girls
530
830
362
45
0.27
All
1 052
1 722
729
45
0.62
Boys
534
871
376
46
0.55
girls
518
851
353
45
0.92
All
2 373
1 020
110
18
0.98
Boys
1 202
526
53
18
0.62
girls
1 171
494
57
18
0.58
All
1 246
1 679
578
40
0.76
Boys
610
881
290
41
0.35
girls
636
798
288
40
0.16
rs1260333
rs1260326
rs10105606
rs2954029
GCKR
GCKR
LPL
TRIB1
2
2
8
8
T/C
T/C
C/A
T/A
Chi square*
p value*
2.70
0.26
0.35
0.84
0.21
0.90
0.561
0.75
3.66
0.16
rs1748195
rs964184
ANGPTL3
APOA5-A4-C3-A1 cluster
1
11
C/G
C/G
All
2 064
1 230
209
24
0.15
Boys
1 052
620
109
24
0.17
girls
1 012
610
100
24
0.52
All
2 121
1 208
174
22
0.91
Boys
1 087
606
88
22
0.77
girls
1 034
602
86
22
0.89
Abbreviations: MAF: minor allele frequency. H-W-P: p value for Hardy-Weinberg equilibrium test.
C/C, homozygous for major allele; C/R, heterozygous for minor allele; R/R, homozygous for minor allele.
*
The Chi square and p values for comparing the genotype distribution between boys and girls were shown.
0.25
0.88
0.37
0.83
Online Supplementary Table 4 Results of power calculation for seven SNPs in Chinese pediatric population.
Specific
minor
Major
allele
/minor
SNP
rs2144300
gene
GALNT2
Chr.
1
allele
C/T
position
230,294,916
minor
in
allele
CEU,
CHB,
MAF
MAF
C, 0.417
effect
in
T, 0.222
effect
lipid trait
HDL-C
allele,
allele,
beta-coefficient
per
beta-coefficient per effect
Power
effect allele in children
allele in adults (reference)
(%)
(Tikkanen et al., 2011)
T, 1.11mg/dl (Willer et
*
a
power
for
children
(%)
87.7
G , -0.0158mmol/L
44.1
84.2
-
-
99.8
-
-
69.0
T, 0.0494mmol/L
69.1
>99.9
T, 0.0616(natural log)
>99.9
al., 2008)
TG
C, 4.25mg/dl (Willer et
al., 2008)
rs1260333
GCKR
2
T/C
27,748,624
T, 0.415
C, 0.389
TG
C, -0.054 (natural log)
value (Waterworth et al.,
2010)
rs1260326
GCKR
2
T/C
27,730,940
T, 0.400
C, 0.400
TC
C, -1.91mg/dl (Teslovich
et al., 2010)
TG
C, -8.76mg/dl (Teslovich
et al., 2010)
C,
-0.12
value
s.d.
units
>99.9
-
-
99.7
-
-
99.7
A, 0.0401(natural log)
95.7
(Kathiresan et al., 2009)
rs10105606
LPL
8
A/C
19,827,848
A, 0.276
A, 0.167
TG
C, 0.067 (natural log)
value (Waterworth et al.,
2010)
rs2954029
TRIB1
8
T/A
126,490,972
T, 0.383
A, 0.411
TG
A, 5.64mg/dl (Teslovich
et al., 2010)
T, -0.04 (natural log)
value (Waterworth et al.,
value
95.6
-
-
2010)
LDL-C
T, -0.015 (natural log)
59.8
-
-
>99.9
-
-
99.9
-
-
value (Waterworth et al.,
2010)
TG
T,
-0.11
s.d.
units
(Kathiresan et al., 2009)
rs1748195
ANGPTL3
1
G/C
63,049,593
G, 0.325
G, 0.233
TG
C, 7.12 mg/dl (Willer et
al., 2008)
rs964184
APOA5-A4-
11
G/C
116,648,917
G, 0.108
G, 0.244
TC
-
-
Tb, 0.0672mmol/L
73.1
LDL-C
-
-
Tb, 0.0411 mmol/L
39.8
TC
G, 4.68mg/dl (Teslovich
>99.9
G, 0.121 mmol/L
>99.9
93.9
G, 0.0737 mmol/L
>99.9
99.2
G,-0.0388 mmol/L
93.7
>99.9
-
-
>99.9
G,
C3-A1
cluster
et al., 2010)
LDL-C
G, 2.85mg/dl (Teslovich
et al., 2010)
HDL-C
G, -1.5mg/dl (Teslovich
et al., 2010)
G,
-0.17
s.d.
units
(Kathiresan et al., 2009)
TG
G, 16.95mg/dl (Teslovich
et al., 2010)
0.131(natural
log)
value
Chr.: chromosome. CEU: Utah residents with Northern and Western European ancestry from the CEPH collection. CHB: Han Chinese in Beijing, China. MAF: minor allele
frequency.
The MAFs of CEU and CHB are from HapMap database (http://hapmap.ncbi.nlm.nih.gov/)
>99.9
TG: triglycerides; TC: total cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.
*
We referred to the study reported by Tikkanen E., et al. in children, and used the effects from children to calculate the specific power for our children population. The SNP
in high linkage disequilibrium (LD) (r2>0.75) with our selected SNPs was cited. Effect sizes for HDL-C, LDL-C, and total cholesterol are in mmol/L and for TG natural
log-transformed mmol/L.
a
The tested SNP is rs4846914, which is in a high LD with rs2144300 (r2=0.878).
b
The tested SNP is rs3850634, which is in a high LD wi
Online Supplementary Table 5 Association of the seven SNPs with TG, TC, HDL-C and LDL-C
all a
boys b
girls b
lipid trait
SNP
minor allele
effect
p value
effect
p value
effect
p value
TG * (mg/dl)
rs2144300
T
-0.03
9.30×10-3
-0.03
0.18
-0.04
0.03
rs1260333
C
-0.07
6.20×10-11
-0.06
2.27×10-5
-0.07
7.60×10-7
-11
-0.06
7.16×10
-5
-0.07
2.48×10-7
TC (mg/dl)
rs1260326
C
-0.07
8.73×10
rs10105606
A
-0.03
0.010
-0.03
0.10
-0.04
0.02
rs2954029
A
0.02
0.030
0.03
0.06
0.02
0.27
rs1748195
G
-0.03
0.016
-0.03
0.06
-0.03
0.11
0.08
7.53×10-7
rs964184
G
0.09
2.33×10
rs2144300
T
-0.04
0.97
rs1260333
HDL-C (mg/dl)
C
-2.17
-13
0.10
3.09×10
-8
-1.99
0.13
2.00
0.16
3.30×10
-3
-2.68
0.008
-1.33
0.21
-3
-2.40
0.019
-1.50
0.16
-1.03
rs1260326
C
-2.12
4.39×10
rs10105606
A
0.36
0.71
rs2954029
A
2.58
6.36×10
rs1748195
G
-1.24
rs964184
G
rs2144300
0.44
1.97
0.16
2.96
0.005
2.21
0.04
0.15
-1.67
0.16
-0.84
0.50
1.83
0.040
2.29
0.06
1.07
0.40
T
0.71
0.042
0.31
0.53
1.02
0.04
rs1260333
C
0.34
0.20
0.08
0.83
0.75
0.04
rs1260326
C
0.41
0.13
0.22
0.57
0.76
0.04
0.95
0.06
1.65
5.74×10-4
-0.12
0.76
-0.36
0.33
-0.90
0.042
-0.44
0.31
-1.26
0.006
-0.88
0.05
rs10105606
A
1.19
6.66×10
rs2954029
A
-0.25
0.36
rs1748195
G
-0.67
0.031
rs964184
G
-0.97
2.55×10
-4
-4
-3
LDL-C (mg/dl)
rs2144300
T
-0.37
0.67
-1.53
0.20
0.91
0.49
rs1260333
C
-1.60
0.017
-2.30
0.013
-0.72
0.46
rs1260326
C
-1.69
0.013
-2.25
0.015
-0.94
0.34
rs10105606
A
-0.58
0.51
-2.03
0.10
0.91
0.48
rs2954029
A
2.25
1.09×10-3
2.53
0.008
1.96
0.05
rs1748195
G
-0.07
0.93
-0.46
0.67
0.28
0.81
2.77
0.013
1.62
0.17
rs964184
G
2.25
5.51×10
-3
Abbreviations: TG: triglycerides; TC: total cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.
Effects are measured as additive effects, which correspond to the average change in phenotype when the major allele is replaced by the minor allele.
*
TG levels were natural logarithmically transformed for normal distribution.
a
p values were calculated with adjustment for age, sex, BMI and puberty stage under the additive model.
b
p values were calculated with adjustment for age, BMI and puberty stage under the additive model.
p values <0.05 are shown in bold.
Online Supplementary Table 6 Association of the seven SNPs with TG, TC, HDL-C and LDL-C for obese and non-obese groups.
non-obese **
Obese **
lipid trait
SNP
minor allele
effect
p value
effect
p value
TG * (mg/dl)
rs2144300
T
-0.05
0.06
-0.03
0.08
rs1260333
C
-0.08
1.16×10-5
-0.06
1.08×10-6
rs1260326
C
-0.07
1.30×10-4
-0.07
1.65×10-7
rs10105606
A
-0.03
0.13
-0.03
0.13
rs2954029
A
0.03
0.16
0.02
0.10
rs1748195
G
-0.04
0.05
-0.02
0.15
0.09
1.24×10-8
TC (mg/dl)
HDL-C (mg/dl)
-5
rs964184
G
0.10
1.54×10
rs2144300
T
-2.08
0.19
1.02
0.41
rs1260333
C
-2.84
0.016
-1.73
0.06
rs1260326
C
-2.27
0.06
-1.95
0.039
rs10105606
A
-1.72
0.25
1.67
0.19
rs2954029
A
3.59
0.003
2.01
0.036
rs1748195
G
-4.09
0.003
0.18
0.87
rs964184
G
3.45
0.017
0.95
0.40
rs2144300
T
0.56
0.29
0.79
0.09
rs1260333
C
0.31
0.44
0.44
0.22
rs1260326
C
0.37
0.35
0.52
0.15
rs10105606
A
0.43
0.39
1.37
0.005
rs2954029
A
0.54
0.18
-0.66
0.07
rs1748195
G
-1.29
0.005
-0.39
0.35
rs964184
G
-0.58
0.23
-1.14
0.008
LDL-C (mg/dl)
rs2144300
T
-2.15
0.13
0.56
0.62
rs1260333
C
-2.12
0.045
-1.30
0.13
rs1260326
C
-1.80
0.09
-1.60
0.07
rs10105606
A
-1.62
0.22
0.29
0.81
rs2954029
A
2.30
0.033
2.18
0.014
rs1748195
G
-2.82
0.021
1.33
0.19
rs964184
G
2.67
0.038
1.95
0.06
Abbreviations: TG: triglycerides; TC: total cholesterol; HDL-C: high density lipoprotein cholesterol; LDL-C: low density lipoprotein cholesterol.
Effects are measured as additive effects, which correspond to the average change in phenotype when the major allele is replaced by the minor allele.
*
TG levels were natural logarithmically transformed for normal distribution.
**
p values were calculated with adjustment for sex, age and puberty stage under the additive model.
p values <0.05 are shown in bold.
Online Supplementary Table 7 Association of candidate SNPs in dyslipidemia and nondyslipidemia individuals stratified by non-obese and obese.
nondyslipidemia
dyslipidemia
minor
group
SNP
Chr.
gene
allele
C/C
C/R
R/R
C/C
C/R
R/R
OR(95%CI)
p value
non-obese
rs2144300
1
GALNT2
T
1169
510
63
376
134
17
0.86(0.72-1.04)
0.12
rs1260333
2
GCKR
C
533
828
381
179
252
96
0.87(0.76-1.00)
0.047
rs1260326
2
GCKR
C
524
846
372
180
253
94
0.85(0.74-0.98)
0.026
rs10105606
8
LPL
A
1182
513
47
359
154
14
0.98(0.81-1.18)
0.83
rs2954029
8
TRIB1
A
623
816
303
157
282
88
1.13(0.98-1.30)
0.10
rs1748195
1
ANGPTL3
G
1038
606
98
304
188
35
1.09(0.92-1.28)
0.32
APOA5-A4-C3-A1
obese
rs964184
11
cluster
G
1053
606
83
283
205
39
1.28(1.09-1.51)
0.003
rs2144300
1
GALNT2
T
521
218
23
329
120
14
0.88(0.70-1.11)
0.27
rs1260333
2
GCKR
C
198
384
180
151
224
88
0.76(0.64-0.90)
0.002
rs1260326
2
GCKR
C
203
381
178
143
236
84
0.78(0.66-0.93)
0.006
rs10105606
8
LPL
A
510
223
29
317
126
20
0.94(0.76-1.17)
0.58
rs2954029
8
TRIB1
A
284
372
106
181
204
78
1.04(0.87-1.24)
0.64
rs1748195
1
ANGPTL3
G
432
289
41
284
144
35
0.92(0.76-1.13)
0.43
G
513
226
23
268
166
29
1.48(1.20-1.82)
2.11×10-4
APOA5-A4-C3-A1
rs964184
11
cluster
Abbreviations: Chr, chromosome.
C/C, homozygous for major allele; C/R, heterozygous for minor allele; R/R, homozygous for minor allele.
p values with adjusted age, sex, and puberty stage are displayed under the additive model, and p<0.05 are shown in bold.
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