Prospective association of childhood BMI trajectory and polygenic genetic risk with puberty timing

Abstract

Objective To examine pubertal timing across body mass index (BMI) trajectory under polygenic susceptibility in boys and girls, and to provide a reference basis for children’ s adolescent development deviation form early intervention strategies.

Methods All the participants were recruited from 1 to 3 grade in 2016 from 2 Bengbu primary school and were followed up for 3 consecutive years. The study comprised 997 children (418 boys) with available data for height, weight, BMI, breast Tanner stages and testicular volume annually. The polygenic risk score (PRS) was computed based on 17 SNPs derived from published genome- wide association studies for early pubertal timing. Group-based trajectory model (GBTM) was used to identified BMI trajectory in children. Accelerated failure time model (AFT) was used to examine associations of different BMI trajectory and polygenic risk with pubertal development in boys and girls.

Results Classes of BMI trajectory were persistently healthy weight, persistently overweight and persistently obesity. Adjusted concomitant variables, boys with persistently obesity exhibited 6.10-mo delay of testicular volume in low polygenic risk group (adjusted TR = 1.05, P =0.04). Compared with the girls in persistently healthy weight group, the girls with low PRS were persistently overweight or obesity, which was associated with thelarche age 3.42 and 6.84-mo earlier, respectively (adjusted TR = 0.97, 0.94, P<0.01). Persistently overweight or obesity in girls with moderate PRS was associated with an earlier age of thelarche timing of 6.72 and 8.96-mo, respectively (adjusted TR = 0.94, 0.92, P<0.01). At high PRS groups, the persistently obese girls were found to have a more advanced age (10.80 and 12.96-mo, respectively) of thelarche (adjusted TR = 0.90, 0.88, P<0.01).

Conclusion Persistently overweight and obesity is associated with early thelarche in girls, but persistently obesity may increase delayed puberty risk in boys with low polygenic risk.

Abstract

【摘要】 目的 探讨童年期体质量指数 (BMI) 轨迹与多基因遗传风险对男女童青春期发育启动的影响, 为儿童青春 期发育偏离早期干预策略提供参考依据。 方法 选择蚌埠市 2 所城区小学的 1 263 名一至三年级学生, 建立儿童生长发 育队列。于 2016 年 3 月进行基线调査, 2017—2019 年分别开展随访调査, 共纳人 997 名学生, 包括身髙、体重, 计算腿I、 女童乳房 Tanner 分期和男童睾丸容积。采用群组轨迹模型识别童年期BMI生长轨迹, 使用加速失效时间模型分析童年期 BMI 轨迹对男女童青春期发动的影响。根据测得的 17 个青春期相关 SNP 计算多基因遗传风险。 结果 BMI 轨迹分为 3 类, 分别为持续正常组、持续超重组和持续肥胖组。控制协变量后, 仅在低青春期发育多基因遗传风险评分 (PRS) 组男童 中观察到与持续正常组相比, 持续肥胖儿童睾丸发育年龄延迟 6.10 个月 (校正后 TR =1.05, P = 0.04)。与持续正常组相 比, 具有低 PRS 和中等 PRS 的女童持续超重或肥胖分别与乳房启动年龄提前 3.42 和6.84个月有关 (校正后 TR 值分别为 0.97和0.94, P 值均<0.01); 具有中等 PRS 的女童持续超重或肥胖分别与乳房启动年龄提前 6.72 和 8, 96 个月有关 (校正 后 TR 值分别为 0.94 和 0.92, P 值均<0.01); 在髙 PRS 的女童中, 发现持续超重或肥胖儿童乳房启动年龄提前更多, 分别为 10.80 和 12.96 个月 (校正后 TR 值分别为 0.90 和 0.88, P 值均<0.01)。 结论 持续超重和肥胖与女童乳房发育提前有关, 而持续肥胖与低遗传风险男童睾丸发育延迟有关。