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Genetics

Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence

Influence of Loci Identified by Genome-Wide Association Studies

  1. Marcel den Hoed1,
  2. Ulf Ekelund1,2,
  3. Søren Brage1,
  4. Anders Grontved3,
  5. Jing Hua Zhao1,
  6. Stephen J. Sharp1,
  7. Ken K. Ong1,
  8. Nicholas J. Wareham1 and
  9. Ruth J.F. Loos1
  1. 1Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K.;
  2. 2School of Health and Medical Sciences, Örebro University, Örebro, Sweden;
  3. 3Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark.
  1. Corresponding author: Ruth J.F. Loos, ruth.loos{at}mrc-epid.cam.ac.uk.
Diabetes 2010 Nov; 59(11): 2980-2988. https://doi.org/10.2337/db10-0370
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  • FIG. 1.
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    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.
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    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.

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    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.

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  • 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 ± 0.49.6 ± 0.415.5 ± 0.515.5 ± 0.5
    Tanner stage (1–5)1.03 ± 0.171.29 ± 0.504.30 ± 0.894.35 ± 0.68
    BMI (kg/m2)17.1 ± 2.217.1 ± 2.620.5 ± 2.520.5 ± 2.7
    Weight (kg)33.3 ± 6.133.1 ± 6.962.5 ± 10.156.2 ± 8.3
    Height (cm)139.1 ± 6.6138.7 ± 6.7174.3 ± 7.6165.3 ± 6.0
    Sum of skinfolds (mm)29.5 ± 14.437.0 ± 18.132.1 ± 15.347.8 ± 17.0
    Waist circumference (cm)59.4 ± 5.558.4 ± 6.671.3 ± 5.966.8 ± 5.8
    Physical activity (cpm)740.2 ± 235.7613.2 ± 188.3558.8 ± 238.5455.0 ± 166.4
    Moderate/vigorous physical activity (% registered time)11.1 ± 5.27.9 ± 3.88.0 ± 4.96.2 ± 3.5
    % normal weight80.885.786.088.2
    % overweight, nonobese12.19.18.89.3
    % obese7.15.25.12.5
    • 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 geneBMISum of skinfoldsWaist circumferenceHeight
    Effect size (SD/allele)SEPEffect size (SD/allele)SEPEffect size (SD/allele)SEPEffect size (SD/allele)SEP
    rs2815752NEGR10.0810.038.9 × 10−30.0520.030.060.0620.024.8 × 10−30.0310.030.32
    rs10913469SEC16B0.1360.044.2 × 10−40.1260.032.5 × 10−40.0750.036.8 × 10−3−0.0090.040.82
    rs2605100*LYPLAL10.0120.030.730.0600.033.9 × 10−20.0600.021.0 × 10−2−0.0270.030.42
    rs6548238TMEM180.1480.041.9 × 10−40.1500.042.5 × 10−50.0680.031.6 × 10−20.0850.043.8 × 10−2
    rs7647305ETV50.0480.040.210.0280.030.420.0300.030.270.0340.040.39
    rs10938397GNPDA20.0510.030.080.0610.032.5 × 10−20.0410.020.06−0.0040.030.89
    rs987237*TFAP2B0.0690.040.060.0420.030.210.0560.033.5 × 10−2−0.0250.040.50
    rs545854*MSRA−0.0800.040.070.0010.040.99−0.0500.030.10−0.0330.040.47
    rs1488830BDNF0.0370.040.350.0280.030.410.0030.030.910.0260.040.52
    rs925946BDNF0.0570.030.080.0650.032.7 × 10−20.0340.020.140.0520.030.12
    rs10838738MTCH2−0.0170.030.61−0.0120.030.670.0010.020.97−0.0420.030.21
    rs7138803BCDIN3D0.0450.030.130.0290.030.280.0230.020.290.0780.031.3 × 10−2
    rs10146997*NRXN30.0220.040.560.0290.030.380.0180.030.510.0390.040.31
    rs8055138SH2B10.0120.030.680.0310.030.260.0040.020.870.0040.030.91
    rs1121980FTO0.0200.030.470.0330.030.220.0040.020.850.0090.030.77
    rs17782313MC4R0.0130.040.720.0150.030.65−0.0060.030.830.0040.040.93
    rs11084753KCTD150.0200.030.540.0230.030.410.0090.020.690.0390.030.24
    GPS-120.0440.017.1 × 10−60.0430.017.2 × 10−70.0250.013.4 × 10−40.0230.012.4 × 10−2
    GPS-170.0340.013.6 × 10−50.0390.011.7 × 10−70.0220.011.7 × 10−40.0120.010.15
    • 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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Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence
Marcel den Hoed, Ulf Ekelund, Søren Brage, Anders Grontved, Jing Hua Zhao, Stephen J. Sharp, Ken K. Ong, Nicholas J. Wareham, Ruth J.F. Loos
Diabetes Nov 2010, 59 (11) 2980-2988; DOI: 10.2337/db10-0370

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Genetic Susceptibility to Obesity and Related Traits in Childhood and Adolescence
Marcel den Hoed, Ulf Ekelund, Søren Brage, Anders Grontved, Jing Hua Zhao, Stephen J. Sharp, Ken K. Ong, Nicholas J. Wareham, Ruth J.F. Loos
Diabetes Nov 2010, 59 (11) 2980-2988; DOI: 10.2337/db10-0370
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