Background
Methods
Characterization of Study Subjects
Subjects
Obesity families
sub-group | n participants | sex (M/F) | mean age (y) ± SD | mean BMI (kg/m)2 ± SD | |
---|---|---|---|---|---|
Group
|
parents
| 1,522 | 761/761 | 42.55 ± 5.96 | 30.37 ± 6.28 |
children | 1,041 | 477/564 | 13.88 ± 3.71 | 31.11 ± 6.051,2
| |
obese children and | |||||
case-control
| adolescents | 336 | 153/183 | 10.74 ± 2.75 | 28.29 ± 4.811
|
obese adults | 987 | 361/626 | 46.31 ± 14.74 | 36.03 ± 5.39 | |
underweight and normal | |||||
weight controls | 588 | 235/353 | 25.28 ± 4.41 | 19.34 ± 1.94 | |
KORA S3/S4
| BMI ≥ 30 kg/m2
| 1,849 | 876/973 | 54.47 ± 0.29 | 33.58 ± 0.08 |
BMI < 30 kg/m2
| 6,420 | 3,267/3,153 | 47.92 ± 0.17 | 25.23 ± 0.04 | |
SHIP
| BMI ≥ 30 kg/m2
| 1,099 | 531/568 | 54.90 ± 14.34 | 33.55 ± 3.29 |
BMI < 30 kg/m2
| 3,201 | 1,582/1,619 | 48.04 ± 16.69 | 25.13 ± 2.94 |
Case-control studies
KORA
SHIP
Genotyping and SNPs selection
In silico analysis of GIPR polymorphisms
Statistical analysis
Results
Initial family-based association studies
SNP | physical position | n genotyped families | localization | risk-allele | transmitted1
| non- transmitted | p-value |
---|---|---|---|---|---|---|---|
Putative | |||||||
rs8111428
| 50859941 | 579 | promoter | G | 403 | 329 | 0.0016 |
rs23023082
| 50864409 | 541 | Intron 1 | A | 395 | 329 | 0.0089 |
rs1800437
| 50873232 | 761 | Exon 12 | G | 1,644 | 1,599 | 0.0760 |
rs81114282
| rs2302382 | |
---|---|---|
rs2302382
2
| 0.71 | - |
rs1800437
3
| 0.039 | 0.039 |
rs8111428 | rs2302382 | rs1800437 | transmitted | non- transmitted | estimated frequency of the haplotype | p-value |
---|---|---|---|---|---|---|
A | A | G | 18.02 | 30.01 | 0.04 | 0.179 |
A | C | G | 325.20 | 326.90 | 0.57 | 0.919 |
A | C | C | 103.80 | 129.10 | 0.16 | 0.054 |
G
|
A
|
G
|
123.80
|
86.10
|
0.21
|
0.003
|
G | A | C | 7.20 | 6.90 | 0.01 | 0.179 |
G | C | G | 8.00 | 7.00 | 0.02 | 0.179 |
Validation studies in case-control samples and in cross-sectional population-based samples
SNP | Group | genotypes, n (frequency) | frequency of allele | effect size estimate – odds ratio (95%CI)1
| p-value1
| |||
---|---|---|---|---|---|---|---|---|
obese children and | ||||||||
rs8111428
| adolescents | 199 (0.592) AA | 124 (0.369) AG | 13 (0.039)GG | 0.777 A | 0.223 G | ORAG 1.24 (1.04;1.49) | 0.019 |
obese adults | 633 (0.642) AA | 308 (0.312) AG | 45 (0.046)GG | 0.798 A | 0.202 G | ORGG 1.54 (1.07;2.33) | ||
controls | 396 (0.676) AA | 176 (0.300) AG | 14 (0.024) GG | 0.826 A | 0.174 G | |||
obese children and | ||||||||
rs2302382
| adolescents | 176 (0.587) CC | 105 (0.350) AC | 19 (0.063) AA | 0.762 C | 0.238 A | ORAC 1.24 (1.04;1.48) | 0.014 |
obese adults | 597 (0.605) CC | 337 (0.341) AC | 53 (0.054) AA | 0.776 C | 0.224 A | ORAA 1.54 (1.09;2.19) | ||
controls | 385 (0.655) CC | 181 (0.308) AC | 22 (0.037) AA | 0.809 C | 0.191 A | |||
obese children and | ||||||||
rs1800437
| adolescents | 208 (0.619) GG | 113 (0.336) CG | 15 (0.045) CC | 0.787 G | 0.213 C | ORCG 1.11 (0.94;1.32) | 0.219 |
obese adults | 625 (0.634) GG | 319 (0.324) CG | 42 (0.043) CC | 0.796 G | 0.204 C | ORGG 1.24 (0.88;1.73) | ||
controls | 355 (0.605) GG | 200 (0.341) CC | 32 (0.055) CC | 0.775 G | 0.225 C |
Group | genotypes, n (frequency) | Allele frequency | effect size estimate (95%CI)1
| p-value1
| ||||
---|---|---|---|---|---|---|---|---|
CC | CA | AA | C | A | ||||
KORA
| BMI ≥ 30 kg/m2
| 1,103 (0.597) | 644 (0.348) | 102 (0.055) | 0.771 | 0.229 | βA 0.12 | 0.136 |
BMI <30 kg/m2
| 3,993 (0.622) | 2,117 (0.330) | 310 (0.048) | 0.787 | 0.213 | (-0.04; 0.28) | ||
SHIP
| BMI ≥ 30 kg/m2
| 645 (0.640) | 332 (0.329) | 31 (0.031) | 0.805 | 0.195 | βA -0.27 (-0.52; -0.24) | 0.031 |
BMI <30 kg/m2
| 1,842 (0.622) | 995 (0.336) | 126 (0.042) | 0.790 | 0.210 |