Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence
Influence of Loci Identified by Genome-Wide Association Studies
Article Figures & Tables
Figures
- FIG. 1.
Distribution of the GPS-17 and cumulative effects of the effect alleles from the 17 obesity susceptibility variants on inverse normally transformed BMI, sum of skinfolds, and waist circumference.
- FIG. 2.
Meta-analysis for summary statistics of the association between variants in the obesity susceptibility loci with BMI in the EYHS, CHP (28), and ALSPAC (20). I2 and P values for heterogeneity between cohorts are provided. For associations within cohorts, effect sizes (B) and 95% CIs are shown; for the meta-analysis, P values for effect sizes are additionally provided.
- FIG. 3.
Association of variants in the obesity susceptibility loci with BMI after meta-analysis in a maximal sample of 13,071 (NEGR1, TMEM18, GNPDA2, MTCH2, SH2B1, FTO, MC4R, and KCTD15) or 8,120 (SEC16B, ETV5, BDNF, and BCIN3D) children and adolescents compared with 20,431 adults from the EPIC-Norfolk cohort. Effect sizes (B) and 95% CIs are shown; I2 and P values for heterogeneity between age-groups are additionally provided.
Tables
- TABLE 1
Descriptive characteristics of children and adolescents of the EYHS stratified by sex
Children (n = 1,252) Adolescents (n = 790) Male (n = 593) Female (n = 659) Male (n = 351) Female (n = 439) Age (years) 9.7 ± 0.4 9.6 ± 0.4 15.5 ± 0.5 15.5 ± 0.5 Tanner stage (1–5) 1.03 ± 0.17 1.29 ± 0.50 4.30 ± 0.89 4.35 ± 0.68 BMI (kg/m2) 17.1 ± 2.2 17.1 ± 2.6 20.5 ± 2.5 20.5 ± 2.7 Weight (kg) 33.3 ± 6.1 33.1 ± 6.9 62.5 ± 10.1 56.2 ± 8.3 Height (cm) 139.1 ± 6.6 138.7 ± 6.7 174.3 ± 7.6 165.3 ± 6.0 Sum of skinfolds (mm) 29.5 ± 14.4 37.0 ± 18.1 32.1 ± 15.3 47.8 ± 17.0 Waist circumference (cm) 59.4 ± 5.5 58.4 ± 6.6 71.3 ± 5.9 66.8 ± 5.8 Physical activity (cpm) 740.2 ± 235.7 613.2 ± 188.3 558.8 ± 238.5 455.0 ± 166.4 Moderate/vigorous physical activity (% registered time) 11.1 ± 5.2 7.9 ± 3.8 8.0 ± 4.9 6.2 ± 3.5 % normal weight 80.8 85.7 86.0 88.2 % overweight, nonobese 12.1 9.1 8.8 9.3 % obese 7.1 5.2 5.1 2.5 Data are means ± SD. Obese, BMI ≥95th percentile; overweight but nonobese, BMI ≥ 85th percentile and <95th percentile; normal weight, BMI <85th percentile. For moderate and vigorous intensity physical activity, data were available for 408 and 462 children (male and female, respectively) and 166 and 247 adolescents.
- TABLE 2
Associations of the individual obesity susceptibility SNPs and the GPS-12 and GPS-17 with anthropometric traits in children and adolescents of the EYHS (n = 2,042)
SNP nearest gene BMI Sum of skinfolds Waist circumference Height Effect size (SD/allele) SE P Effect size (SD/allele) SE P Effect size (SD/allele) SE P Effect size (SD/allele) SE P rs2815752 NEGR1 0.081 0.03 8.9 × 10−3 0.052 0.03 0.06 0.062 0.02 4.8 × 10−3 0.031 0.03 0.32 rs10913469 SEC16B 0.136 0.04 4.2 × 10−4 0.126 0.03 2.5 × 10−4 0.075 0.03 6.8 × 10−3 −0.009 0.04 0.82 rs2605100* LYPLAL1 0.012 0.03 0.73 0.060 0.03 3.9 × 10−2 0.060 0.02 1.0 × 10−2 −0.027 0.03 0.42 rs6548238 TMEM18 0.148 0.04 1.9 × 10−4 0.150 0.04 2.5 × 10−5 0.068 0.03 1.6 × 10−2 0.085 0.04 3.8 × 10−2 rs7647305 ETV5 0.048 0.04 0.21 0.028 0.03 0.42 0.030 0.03 0.27 0.034 0.04 0.39 rs10938397 GNPDA2 0.051 0.03 0.08 0.061 0.03 2.5 × 10−2 0.041 0.02 0.06 −0.004 0.03 0.89 rs987237* TFAP2B 0.069 0.04 0.06 0.042 0.03 0.21 0.056 0.03 3.5 × 10−2 −0.025 0.04 0.50 rs545854* MSRA −0.080 0.04 0.07 0.001 0.04 0.99 −0.050 0.03 0.10 −0.033 0.04 0.47 rs1488830 BDNF 0.037 0.04 0.35 0.028 0.03 0.41 0.003 0.03 0.91 0.026 0.04 0.52 rs925946 BDNF 0.057 0.03 0.08 0.065 0.03 2.7 × 10−2 0.034 0.02 0.14 0.052 0.03 0.12 rs10838738 MTCH2 −0.017 0.03 0.61 −0.012 0.03 0.67 0.001 0.02 0.97 −0.042 0.03 0.21 rs7138803 BCDIN3D 0.045 0.03 0.13 0.029 0.03 0.28 0.023 0.02 0.29 0.078 0.03 1.3 × 10−2 rs10146997* NRXN3 0.022 0.04 0.56 0.029 0.03 0.38 0.018 0.03 0.51 0.039 0.04 0.31 rs8055138 SH2B1 0.012 0.03 0.68 0.031 0.03 0.26 0.004 0.02 0.87 0.004 0.03 0.91 rs1121980 FTO 0.020 0.03 0.47 0.033 0.03 0.22 0.004 0.02 0.85 0.009 0.03 0.77 rs17782313 MC4R 0.013 0.04 0.72 0.015 0.03 0.65 −0.006 0.03 0.83 0.004 0.04 0.93 rs11084753 KCTD15 0.020 0.03 0.54 0.023 0.03 0.41 0.009 0.02 0.69 0.039 0.03 0.24 GPS-12 0.044 0.01 7.1 × 10−6 0.043 0.01 7.2 × 10−7 0.025 0.01 3.4 × 10−4 0.023 0.01 2.4 × 10−2 GPS-17 0.034 0.01 3.6 × 10−5 0.039 0.01 1.7 × 10−7 0.022 0.01 1.7 × 10−4 0.012 0.01 0.15 Results were obtained using multiple linear regression analysis assuming an additive effect while adjusting for sex, age, age-group, country, and maturity. The sum of skinfolds and waist circumference were additionally adjusted for height.
*Located in or near loci identified in GWA studies for waist circumference; all other SNPs were identified in GWA studies for BMI.
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