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  • Original Article
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Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples

International Journal of Obesity volume 37, pages 191–196 (2013)Cite this article

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Abstract

Background:

Meta-analysis of case–control genome-wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.

Objective:

We aimed to validate association of these variants with obesity-related traits in population-based samples.

Design:

Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r2>0.8), with the odds of being overweight and obese, as well as with body mass index (BMI), percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age2 in adults and for sex, age, age group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.

Results:

We had 80% power to detect odds ratios of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P>0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (β=0.013 s.d./allele, P=0.040), but not with any of the remaining obesity-related traits (P>0.3).

Conclusion:

Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.

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Acknowledgements

The authors would like to thank the study teams, who collected the data used in these analyses. We also acknowledge the volunteers, who gave their time to take part in the individual studies. The Fenland study was supported by the Wellcome Trust; the Medical Research Council; the Support for Science Funding programme; and CamStrad. The EPIC Norfolk Study was supported by Cancer Research United Kingdom; and the Medical Research Council. The Whitehall II Study was supported by grants from the Medical Research Council (MRC); the British Heart Foundation; the United Kingdom Health and Safety Executive; the United Kingdom Department of Health; the US National Heart, Lung, and Blood Institute (Grant HL36310); the US National Institute on Aging (Grant AG13196); the US Agency for Health Care Policy and Research (Grant HS06516); and the John D and Catherine T MacArthur Foundation Research Networks on Successful Midlife Development and Socio-economic Status and Health. The MRC Ely Study was supported by the Medical Research Council; and the Wellcome Trust. The Hertfordshire Study was supported by the Medical Research Council UK; and the University of Southampton UK. The EYHS was supported by grants from The Danish Heart Foundation; The Danish Medical Research Council Health Foundation; The Danish Council for Sports Research; The Foundation in Memory of Asta Florida Bolding Renée Andersen; The Faculty of Health Sciences, University of Southern Denmark; and The Estonian Science Foundation (Grant 3277, 5209).

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Authors and Affiliations

  1. MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK

    M den Hoed, J Luan, C Langenberg, U Ekelund, N J Wareham & R J F Loos

  2. MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, UK

    C Cooper, A A Sayer & K Jameson

  3. Department of Epidemiology and Public Health, University College London, London, UK

    M Kumari, M Kivimaki & A D Hingorani

  4. Institute of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark

    A Grøntved

  5. Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK

    K-T Khaw

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  1. M den Hoed
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Correspondence to R J F Loos.

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den Hoed, M., Luan, J., Langenberg, C. et al. Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. Int J Obes 37, 191–196 (2013). https://doi.org/10.1038/ijo.2012.34

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