The effect of GWAS identified BMI loci on changes in body weight among middle-aged danes during a five-year period

Authors

  • C. H. Sandholt,

    Corresponding author
    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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    • Funding agencies: This project was funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). Further funding came from the Danish Council for Independent Research (Medical Sciences). The Inter99 was initiated by Torben Jorgensen (PI), Knut Borch-Johnsen (co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee comprises the former two and Charlotta Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association.

  • K. H. Allin,

    Corresponding author
    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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    • Funding agencies: This project was funded by the Lundbeck Foundation and produced by The Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care (LuCamp, www.lucamp.org). The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). Further funding came from the Danish Council for Independent Research (Medical Sciences). The Inter99 was initiated by Torben Jorgensen (PI), Knut Borch-Johnsen (co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee comprises the former two and Charlotta Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association.

  • U. Toft,

    1. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
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  • A. Borglykke,

    1. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
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  • R. Ribel-Madsen,

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • T. Sparso,

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • J. M. Justesen,

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • M. N. Harder,

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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  • T. Jørgensen,

    1. Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
    2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    3. Faculty of Medicine, University of Aalborg, Aalborg, Denmark
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  • T. Hansen,

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    3. Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark
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  • O. Pedersen

    1. The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    2. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
    3. Faculty of Health Sciences, University of Aarhus, Aarhus, Denmark
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  • Disclosure: The authors declare that there are no conflicts of interest associated with this manuscript.

  • Author contributions: CS and KA were responsible for study design and data analysis. RR, TS, JJ, and MH were responsible for genotype data generation. CS, KA, UT, AB, and TJ were responsible for data interpretation. TJ was PI initiating the study cohort. TH and OP were PIs initiating the genotyping project. CS and KA were responsible for writing the manuscript. All authors were involved in reviewing the manuscript and had final approval of the submitted and published versions.

  • C. H. Sandholt and K. H. Allin contributed equally to this article.

Abstract

Objective

Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations.

Methods

Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS.

Results

The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10−12), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed.

Conclusion

The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.

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