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.
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.
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 × 10−4) and VAT increased 0.021 SDS (95% CI: 0.009 to 0.032, P-value: 4.68 × 10−4). The adult BMI risk score was positively associated with SAT (0.022 SDS increase, CI: 0.015 to 0.029, P-value: 1.33 × 10−9) and VAT (0.017 SDS increase, CI: 0.010 to 0.025, P-value: 7.00 × 10−6) and negatively with VAT/SAT ratio (−0.012 SDS decrease, CI: −0.019 to −0.006, P-value: 2.88 × 10−4). The liver fat risk score was associated with liver fat fraction (0.121 SDS, CI: 0.086 to 0.157, P-value: 2.65 × 10−11). Rs7185735 (SAT) was associated with SAT (0.151 SDS, CI: 0.087 to 0.214, P-value: 3.00 × 10−6) and VAT/SAT ratio (−0.126 SDS, CI: −0.186 to −0.065, P-value: 4.70 × 10−5). 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.
Genetic variants associated with BMI, body fat distribution, liver and pericardial fat already affect body fat distribution in childhood.
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The Generation R Study is conducted by the Erasmus Medical Center in close collaboration with the School of Law and Faculty of Social Sciences of the Erasmus University Rotterdam, the Municipal Health Service Rotterdam area, Rotterdam, the Rotterdam Homecare Foundation, Rotterdam, and the Stichting Trombosedienst and Artsenlaboratorium Rijnmond (STAR), Rotterdam. We gratefully acknowledge the contribution of participating mothers, general practitioners, hospitals, midwives and pharmacies in Rotterdam. The generation and management of GWAS genotype data for the Generation R Study were done at the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, The Netherlands. We thank Karol Estrada, Dr Tobias A Knoch, Anis Abuseiris, Luc V de Zeeuw and Rob de Graaf for their help in creating GRIMP, BigGRID, MediGRID and Services@MediGRID/D-Grid (funded by the German Bundesministerium fuer Forschung und Technology; Grants 01 AK 803A-H and 01 IG 07015 G) and for access to their grid computing resources. We thank Mila Jhamai, Manoushka Ganesh, Pascal Arp, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating, managing and QC of the GWAS database. Also, we thank Karol Estrada for their support in creation and analysis of imputed data. The general design of Generation R Study is made possible by financial support from the Erasmus Medical Center, Rotterdam, the Erasmus University Rotterdam, the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands Organisation for Scientific Research (NWO), the Ministry of Health, Welfare and Sport and the Ministry of Youth and Families. This research also received funding from the European Union’s Seventh Framework Programme (FP7/2007–2013), project EarlyNutrition under Grant Agreement No. 289346. VWVJ received an additional grant from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and a Consolidator Grant from the European Research Council (ERC-2014-CoG-648916). JFF has received funding from the European Union’s Horizon 2020 research and innovation programme under Grant Agreement No. 633595 (DynaHEALTH). The study was supported by funding from the European Union’s Horizon 2020 research and innovation programme (733206, LIFECYCLE).
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Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)