Original Article

Integrative Biology

Genetic risk scores for body fat distribution attenuate weight loss in women during dietary intervention

  • International Journal of Obesity volume 42, pages 370375 (2018)
  • doi:10.1038/ijo.2017.279
  • Download Citation
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Abstract

Objective:

The well-established link between body fat distribution and metabolic health has been suggested to act through an impact on the remodeling capacity of the adipose tissue. Remodeling of the adipose tissue has been shown to affect body fat distribution and might affect the ability to lose weight. We aimed to study the effect of weighted genetic risk scores (GRSs) on weight loss based on single-nucleotide polymorphisms (SNPs) associated with waist-hip-ratio adjusted for body mass index (WHRadjBMI).

Design:

We included 707 participants (533 women and 174 men) from the NUGENOB multi-center 10-week diet intervention study with weekly weight measurements. We created 3 GRSs, one including all reported WHRadjBMI SNPs (GRStotal), one including only SNPs with genome-wide significance in women or with significantly greater effect in women (GRSwomen), and one excluding SNPs in the GRSwomen (GRSmen). The data were analyzed in a mixed linear model framework.

Results:

The GRStotal and GRSwomen attenuated weight loss in women. The effect was strongest for the GRSwomen with an effect of 2.21 g per risk allele per day (95% confidence intereval (CI) (0.90;3.52), P=0.0009). Adjustment for WHR, basal metabolic rate or diet compliance did not affect the result. The GRSs had no effect on weight loss in men. The VEGFA rs1358980-T strongly attenuated weight loss in both men and women (β=15.95 g per risk allele per day, (3.16;26.74), P=0.013) and (β=15.95 g per risk allele per day, (2.58;13.53), P=0.004), respectively).

Conclusion:

Our findings suggest that genetic variants influencing body fat distribution attenuate weight loss in women independently on the effect on WHR. The stronger effect of the GRSwomen implies heterogenic effects of the WHRadjBMI variants on weight loss. A strong effect of rs1358980-T in the VEGFA locus suggests that angiogenesis plays a role, but this needs confirmation from functional studies.

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Acknowledgements

The Danish Diabetes Academy supported by the Novo Nordisk Foundation granted 1/3 of the PhD study for MS. KHA received grants from The Danish Diabetes Association and the Novo Nordisk Foundation. We thank the NUGENOB project steering committee, especially Arne Astrup as the main responsible for the dietary intervention, as well as all participants and employees involved in collecting the data from the 8 NUGENOB study centers. We also thank Tina Hvidtfeldt Lorentzen for extraction of the DNA and Jette Bork-Jensen and Vincent Appel for bioinformatic assistance.

Author information

Affiliations

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

    • M Svendstrup
    • , K H Allin
    • , T I A Sørensen
    • , T H Hansen
    • , N Grarup
    • , T Hansen
    •  & H Vestergaard
  2. Danish Diabetes Academy, Odense, Denmark

    • M Svendstrup
  3. Department of Clinical Epidemiology, Bispebjerg and Frederiksberg Hospitals, Frederiksberg, Denmark

    • K H Allin
    •  & T I A Sørensen
  4. Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark

    • T I A Sørensen
  5. Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark

    • T I A Sørensen
  6. Steno Diabetes Center, Copenhagen, Denmark

    • H Vestergaard

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to M Svendstrup.

Supplementary information

Supplementary Information accompanies this paper on International Journal of Obesity website (http://www.nature.com/ijo)