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Epidemiology and Population Health

Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study

International Journal of Obesity volume 39, pages 1001–1009 (2015)Cite this article

Subjects

Abstract

Background:

Genome-wide association studies in adults have identified genetic loci associated with adiposity measures. Little is known about the effects of these loci on growth and body fat distribution from early childhood onwards.

Methods:

In a population-based prospective cohort study among 4144 children, we examined the associations of weighted risk scores combining 29 known genetic markers of adult body mass index (BMI) and 14 known genetic markers of adult waist-hip ratio (WHR) with peak weight velocity, peak height velocity, age at adiposity peak and BMI at adiposity peak in early infancy and additionally with BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area at the median age of 6.0 years (95% range 5.7, 7.8).

Results:

A higher adult BMI genetic risk score was associated with a higher age at adiposity peak in infancy and a higher BMI, total fat mass, android/gynoid fat ratio and preperitoneal fat area in childhood (P=0.05, 1.5 × 10−24, 3.6 × 10−18, 4.0 × 10−11 and 1.3 × 10−5, respectively), with the strongest association for childhood BMI with a 0.04 higher s.d. score BMI (95% confidence interval 0.03, 0.05) per additional risk allele. A higher adult WHR genetic risk score was not associated with infant growth measures or childhood BMI and total fat mass, but was associated with childhood android/gynoid fat ratio and preperitoneal fat area (P<0.05).

Conclusion:

Genetic variants associated with BMI and WHR in adults influence growth patterns and general and abdominal fat development from early childhood onwards.

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Acknowledgements

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. 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, 01 IG 07015 G) 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. VWJ received an additional grant from the Netherlands Organization for Health Research and Development (VIDI 016.136.361).

Author Contributions

SV, CM, JFF and VWVJ designed and conducted the research and wrote the paper. SV analyzed the data. CM, RG, CMR, AH, VWVJ and JFF provided comments and consultation regarding the analyses, interpretation of the results and manuscript. SV, JFF and VWVJ had primary responsibility for final content. All authors gave final approval of the version to be published.

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Authors and Affiliations

  1. The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    S Vogelezang, C Monnereau, R Gaillard, V W V Jaddoe & J F Felix

  2. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    S Vogelezang, C Monnereau, R Gaillard, A Hofman, V W V Jaddoe & J F Felix

  3. Department of Pediatrics, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands

    S Vogelezang, C Monnereau, R Gaillard, V W V Jaddoe & J F Felix

  4. Department of Health Sciences, Faculty of Earth and Life Sciences and EMGO Institute for Health and Care Research, VU University Amsterdam, Amsterdam, the Netherlands

    C M Renders

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  1. S Vogelezang
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Correspondence to J F Felix.

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Vogelezang, S., Monnereau, C., Gaillard, R. et al. Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study. Int J Obes 39, 1001–1009 (2015). https://doi.org/10.1038/ijo.2015.12

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