Table 2. GENERALIZATION.
| GENERALIZATION | |||||||
| children and adolescents (n = 3,525) | adults (n = 25,958) | ||||||
| chromosomal regiona (suggested gene) | SNP (obesity risk effect alleleb) | BMI-SDSd estimator (beta) for effect allele (95% CI) | p-value | BMI estimator (beta) for effect allele (95% CI) | p-value | combined BMI estimator (beta) for effect allele (95% CI)e | combined p-valuee |
| 1q43–q44 (SDCCAG8) | rs10926984 (T) | 0.016 (−0.043;0.076) | 0.59 | K 0.04 (−0.11;0.19) | 0.57 | 0.02 (−0.10; 0.13) | 0.79 |
| E 0.01 (−0.22;0.25) | 0.91 | ||||||
| H −0.05 (−0.31;0.21) | 0.73 | ||||||
| rs12145833 (T) | −0.008 (−0.067;0.050) | 0.78 | K 0.07 (−0.08;0.22) | 0.39 | 0.05 (−0.05;0.16) | 0.33 | |
| S 0.18 (−0.09;0.44) | 0.20 | ||||||
| E 0.01 (−0.22;0.25) | 0.92 | ||||||
| H −0.07 (−0.33;0.19) | 0.60 | ||||||
| rs2783963 (C) | 0.006 (−0.054;0.066) | 0.85 | K 0.03 (−0.12;0.18) | 0.70 | 0.02 (−0.10;0.13) | 0.79 | |
| E 0.01 (−0.23;0.25) | 0.94 | ||||||
| H −0.02 (−0.28;0.24) | 0.90 | ||||||
| 2p25.3 (TMEM18) | rs11127485 (T) | 0.079 (−0.021;0.136) | 0.01 | K 0.37 (0.22;0.52) | 9.26×10−7 | 0.35 (0.25;0.45) | 9.97×10−12 |
| S 0.46 (0.20;0.72) | 0.001 | ||||||
| E 0.19 (−0.04;0.42) | 0.11 | ||||||
| H 0.38 (0.14;0.63) | 0.002 | ||||||
| 8p23.1 (TNKS/MSRA) | rs17150703 (A) | −0.028 (−0.103;0.047) | 0.46 | K −0.12 (−0.31;−0.06) | 0.19 | −0.10 (−0.23;0.03) | 0.12 |
| S −0.16 (−0.49;0.18) | 0.37 | ||||||
| E 0.01 (−0.28;0.31) | 0.93 | ||||||
| H −0.13 (−0.44;0.19) | 0.43 | ||||||
| rs13278851 (A) | −0.022 (−0.096;0.052) | 0.56 | K −0.13 (−0.31;0.06) | 0.18 | −0.10 (−0.24;0.04) | 0.15 | |
| E 0.00 (−0.30;0.30) | 0.99 | ||||||
| H −0.13 (−0.44;0.19) | 0.44 | ||||||
| rs516175 (T) | −0.004 (−0.073;0.064) | 0.90 | K −0.03 (−0.20;0.15) | 0.76 | −0.04 (−0.16;0.08) | 0.49 | |
| S −0.13 (−0.45;0.19) | 0.42 | ||||||
| E 0.00 (−0.29;0.26) | 0.99 | ||||||
| H −0.05 (−0.35;0.26) | 0.77 | ||||||
| 16q12.2 (FTO) | rs1558902 (A) | 0.074 (0.031;0.116) | 7.87×10−4 | K 0.29 (0.18;0.40) | 1.34×10−7 | 0.31 (0.24;0.39) | 9.99×10−16 |
| S 0.19 (−0.01;0.39) | 0.07 | ||||||
| E 0.44 (0.27;0.61) | 4.69×10−7 | ||||||
| H 0.34 (0.14;0.53) | 7.76×10−4 | ||||||
| rs9935401 (A) | 0.074 (0.030;0.117) | 9.04×10−4 | K 0.29 (0.18;0.40) | 3.35×10−7 | 0.30 (0.23;0.38) | 7.99×10−15 | |
| S 0.17 (−0.02;0.37) | 0.09 | ||||||
| E 0.44 (0.26;0.60) | 1.36×10−6 | ||||||
| H 0.33 (0.13;0.53) | 0.001 | ||||||
| 18q21.32 (MC4R) | rs17700144 (A) | 0.064 (0.011;0.116) | 0.02 | K 0.10 (−0.03;0.23) | 0.13 | 0.17 (0.08;0.26) | 1.10×10−4 |
| S 0.28 (0.05;0.51) | 0.02 | ||||||
| E 0.18 (−0.02;0.39) | 0.08 | ||||||
| H 0.27 (0.04;0.50) | 0.02 | ||||||
Evidence for quantitative associations (BMI or standard deviation score of BMI (BMI-SDS)) assessed cross-sectionally for 5 loci (10 SNPs) under an additive genetic model. Effect sizes as point estimators and 95% confidence intervals (95% CI), p-values (two-sided) and combined effect estimators and p-values are presented for the adults with abbreviations for the samples: KORA, SHIPc, EPIC-Potsdam, Heinz-Nixdorf Recall Study; all samples are described in detail in Text S1.
aposition and stranding according to dbSNP BUILD 129; Map to Genome Build 36.3;
b(obesity) effect risk alleles as derived from the paediatric extreme obesity GWAS meta-analysis;
cresults for SHIP are based on in silico GWAS data–proxy markers (FTO: rs8050136 for rs9935401, rs1421085 for rs1558902; MC4R: rs476828 for rs17700144); one marker for each region was regarded as sufficient if the others were not available;
dBMI-SDS is a normalized version of BMI expressed as standard deviation score that includes information on age and gender; the results were similar if age and gender were included as covariates;
eby inverse normal method (function metagen in the package meta of R) with weights proportional to the sample size (fixed effects model).