Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.
Diabetes. 2010 Nov;59(11):2980-8. doi: 10.2337/db10-0370. Epub 2010 Aug 19.
Large-scale genome-wide association (GWA) studies have thus far identified 16 loci incontrovertibly associated with obesity-related traits in adults. We examined associations of variants in these loci with anthropometric traits in children and adolescents.
Seventeen variants representing 16 obesity susceptibility loci were genotyped in 1,252 children (mean ± SD age 9.7 ± 0.4 years) and 790 adolescents (15.5 ± 0.5 years) from the European Youth Heart Study (EYHS). We tested for association of individual variants and a genetic predisposition score (GPS-17), calculated by summing the number of effect alleles, with anthropometric traits. For 13 variants, summary statistics for associations with BMI were meta-analyzed with previously reported data (N(total) = 13,071 children and adolescents).
In EYHS, 15 variants showed associations or trends with anthropometric traits that were directionally consistent with earlier reports in adults. The meta-analysis showed directionally consistent associations with BMI for all 13 variants, of which 9 were significant (0.033-0.098 SD/allele; P < 0.05). The near-TMEM18 variant had the strongest effect (0.098 SD/allele P = 8.5 × 10(-11)). Effect sizes for BMI tended to be more pronounced in children and adolescents than reported earlier in adults for variants in or near SEC16B, TMEM18, and KCTD15, (0.028-0.035 SD/allele higher) and less pronounced for rs925946 in BDNF (0.028 SD/allele lower). Each additional effect allele in the GPS-17 was associated with an increase of 0.034 SD in BMI (P = 3.6 × 10(-5)), 0.039 SD, in sum of skinfolds (P = 1.7 × 10(-7)), and 0.022 SD in waist circumference (P = 1.7 × 10(-4)), which is comparable with reported results in adults (0.039 SD/allele for BMI and 0.033 SD/allele for waist circumference).
Most obesity susceptibility loci identified by GWA studies in adults are already associated with anthropometric traits in children/adolescents. Whereas the association of some variants may differ with age, the cumulative effect size is similar.
迄今为止，大规模全基因组关联（GWA）研究已经确定了 16 个与成年人肥胖相关特征无可争议相关的基因座。我们研究了这些基因座中的变异与儿童和青少年人体测量特征的关联。
在欧洲青年心脏研究（EYHS）中，对 1252 名儿童（平均年龄 9.7 ± 0.4 岁）和 790 名青少年（15.5 ± 0.5 岁）的 17 个代表 16 个肥胖易感性基因座的变体进行了基因分型。我们测试了个体变体和遗传易感性评分（GPS-17）与人体测量特征的关联，该评分通过累加效应等位基因的数量来计算。对于 13 个变体，与 BMI 关联的汇总统计数据与先前报告的数据（总计 N[总] = 13071 名儿童和青少年）进行了荟萃分析。
在 EYHS 中，15 个变体与人体测量特征相关或呈趋势，与成人早期的报告方向一致。荟萃分析显示，所有 13 个变体与 BMI 的关联方向一致，其中 9 个具有统计学意义（0.033-0.098 SD/等位基因；P < 0.05）。接近 TMEM18 的变体具有最强的效应（0.098 SD/等位基因 P = 8.5×10(-11)）。与成人早期相比，在 SEC16B、TMEM18 和 KCTD15 中的变体或附近的变体中，BMI 的效应大小在儿童和青少年中往往更为明显（0.028-0.035 SD/等位基因更高），而在 BDNF 中的 rs925946 则更低（0.028 SD/等位基因更低）。GPS-17 中的每个额外的效应等位基因与 BMI 增加 0.034 SD（P = 3.6×10(-5)）、皮褶总和增加 0.039 SD（P = 1.7×10(-7)）和腰围增加 0.022 SD（P = 1.7×10(-4)）相关，这与成人报告的结果相当（BMI 的 0.039 SD/等位基因和腰围的 0.033 SD/等位基因）。
在成人中通过 GWA 研究确定的大多数肥胖易感性基因座已经与儿童/青少年的人体测量特征相关。虽然一些变体的关联可能随年龄而变化，但累积效应大小相似。
