成人肥胖遗传风险评分与磁共振成像评估的儿童腹部、肝脏和心包脂肪的相关性研究。
Associations of adult genetic risk scores for adiposity with childhood abdominal, liver and pericardial fat assessed by magnetic resonance imaging.
机构信息
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
出版信息
Int J Obes (Lond). 2018 Apr;42(4):897-904. doi: 10.1038/ijo.2017.302. Epub 2017 Dec 7.
BACKGROUND
Genome-wide association studies (GWASs) identified single-nucleotide polymorphisms (SNPs) involved in adult fat distribution. Whether these SNPs also affect abdominal and organ-specific fat accumulation in children is unknown.
METHODS
In a population-based prospective cohort study among 1995 children (median age: 9.8 years, 95% range 9.4-10.8), we tested the associations of six genetic risk scores based on previously identified SNPs for childhood body mass index (BMI), adult BMI, liver fat, waist-hip ratio, pericardial fat mass, visceral and subcutaneous adipose tissue ratio (VAT/SAT ratio) and four individual SAT- and VAT-associated SNPs for association with SAT (N=1746), VAT (N=1742), VAT/SAT ratio (N=1738), liver fat fraction (N=1950) and pericardial fat mass (N=1803) measured by magnetic resonance imaging.
RESULTS
Per additional risk allele in the childhood BMI genetic risk score, SAT increased 0.020 s.d. scores (SDS) (95% confidence interval (CI): 0.009 to 0.031, P-value: 3.28 × 10) and VAT increased 0.021 SDS (95% CI: 0.009 to 0.032, P-value: 4.68 × 10). The adult BMI risk score was positively associated with SAT (0.022 SDS increase, CI: 0.015 to 0.029, P-value: 1.33 × 10) and VAT (0.017 SDS increase, CI: 0.010 to 0.025, P-value: 7.00 × 10) and negatively with VAT/SAT ratio (-0.012 SDS decrease, CI: -0.019 to -0.006, P-value: 2.88 × 10). The liver fat risk score was associated with liver fat fraction (0.121 SDS, CI: 0.086 to 0.157, P-value: 2.65 × 10). Rs7185735 (SAT) was associated with SAT (0.151 SDS, CI: 0.087 to 0.214, P-value: 3.00 × 10) and VAT/SAT ratio (-0.126 SDS, CI: -0.186 to -0.065, P-value: 4.70 × 10). After stratification by sex the associations of the adult BMI risk score with SAT and VAT and of the liver fat risk score with liver fat fraction remained in both sexes. Associations of the childhood BMI risk score with SAT, and the adult BMI risk score with VAT/SAT ratio, were present among boys only, whereas the association of the pericardial fat risk score with pericardial fat was present among girls only.
CONCLUSION
Genetic variants associated with BMI, body fat distribution, liver and pericardial fat already affect body fat distribution in childhood.
背景
全基因组关联研究（GWAS）鉴定出与成人脂肪分布相关的单核苷酸多态性（SNP）。这些 SNP 是否也会影响儿童的腹部和器官特异性脂肪积累尚不清楚。
方法
在一项基于人群的前瞻性队列研究中，纳入了 1995 名儿童（中位年龄：9.8 岁，95%范围 9.4-10.8），我们检测了六个基于先前鉴定的 SNP 的遗传风险评分与儿童体重指数（BMI）、成人 BMI、肝脂肪、腰臀比、心包脂肪质量、内脏和皮下脂肪组织比（VAT/SAT 比）和四个与 SAT 和 VAT 相关的个体 SAT 和 VAT 相关 SNP 与 SAT（N=1746）、VAT（N=1742）、VAT/SAT 比（N=1738）、肝脂肪分数（N=1950）和心包脂肪质量（N=1803）的相关性，这些数据均通过磁共振成像测量。
结果
儿童 BMI 遗传风险评分中每增加一个风险等位基因，SAT 增加 0.020 个标准差（SDS）（95%置信区间：0.009 至 0.031，P 值：3.28×10），VAT 增加 0.021 SDS（95%置信区间：0.009 至 0.032，P 值：4.68×10）。成人 BMI 风险评分与 SAT（0.022 SDS 增加，CI：0.015 至 0.029，P 值：1.33×10）和 VAT（0.017 SDS 增加，CI：0.010 至 0.025，P 值：7.00×10）呈正相关，与 VAT/SAT 比呈负相关（-0.012 SDS 减少，CI：-0.019 至 -0.006，P 值：2.88×10）。肝脂肪风险评分与肝脂肪分数相关（0.121 SDS，CI：0.086 至 0.157，P 值：2.65×10）。rs7185735（SAT）与 SAT（0.151 SDS，CI：0.087 至 0.214，P 值：3.00×10）和 VAT/SAT 比（-0.126 SDS，CI：-0.186 至 -0.065，P 值：4.70×10）相关。按性别分层后，成人 BMI 风险评分与 SAT 和 VAT 以及肝脂肪风险评分与肝脂肪分数的相关性在两性中仍然存在。儿童 BMI 风险评分与 SAT 以及成人 BMI 风险评分与 VAT/SAT 比的相关性仅存在于男孩中，而心包脂肪风险评分与心包脂肪的相关性仅存在于女孩中。
结论
与 BMI、体脂分布、肝和心包脂肪相关的遗传变异已影响儿童的体脂分布。
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