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Clinical Studies and Practice

Genes and lifestyle factors in obesity: results from 12 462 subjects from MONICA/KORA

International Journal of Obesity volume 34, pages 1538–1545 (2010)Cite this article

Subjects

Abstract

Background:

Data from meta-analyses of genome-wide association studies provided evidence for an association of polymorphisms with body mass index (BMI), and gene expression results indicated a role of these variants in the hypothalamus. It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure.

Objective:

It was our aim to investigate the association of these genetic factors with BMI in a large homogenous population-based sample to explore the association of these polymorphisms with lifestyle factors related to nutritional intake or energy expenditure, and whether such lifestyle factors could be mediators of the detected single-nucleotide polymorphism (SNP)-association with BMI. It was a further aim to compare the proportion of BMI explained by genetic factors with the one explained by lifestyle factors.

Design:

The association of seven polymorphisms in or near the genes NEGR1, TMEM18, MTCH2, FTO, MC4R, SH2B1 and KCTD15 was analyzed in 12 462 subjects from the population-based MONICA/KORA Augsburg study. Information on lifestyle factors was based on standardized questionnaires. For statistical analysis, regression-based models were used.

Results:

The minor allele of polymorphism rs6548238 C>T (TMEM18) was associated with lower BMI (−0.418 kg m−2, P=1.22 × 10–8), and of polymorphisms rs9935401 G>A (FTO) and rs7498665 A>G (SH2B1) with increased BMI (0.290 kg m−2, P=2.85 × 10–7 and 0.145 kg m−2, P=9.83 × 10–3). The other polymorphisms were not significantly associated. Lifestyle factors were correlated with BMI and explained 0.037% of the BMI variance as compared with 0.006% of explained variance by the associated genetic factors. The genetic variants associated with BMI were not significantly associated with lifestyle factors and there was no evidence of lifestyle factors mediating the SNP–BMI association.

Conclusions:

Our data first confirm the findings for TMEM18 with BMI in a single study on adults and also confirm the findings for FTO and SH2B1. There was no evidence for a direct SNP–lifestyle association.

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Acknowledgements

The MONICA/KORA Augsburg cohort study was financed by the Helmholtz Center Munich, German Research Center for Environmental Health, and supported by grants from the German Federal Ministry of Education and Research (BMBF). This study was funded by the German Research Foundation (DFG, TH-784/2-1, He1446/4-2) and the German Federal Ministry of Education, Science, Research and Technology (National Genome Research Net-2, NGFNplus 01GS0823 and 01GS0820), and was supported by the Munich Center of Health Sciences (McHealth) as part of LMUinnovativ, and a subcontract of the 5 R01DK 075787 by the NIH/NIDDK to Helmholtz Center Munich (to JNH). We thank all members of the Helmholtz Center Munich, Institute of Epidemiology, who were involved in the planning and conduct of the MONICA/KORA Augsburg studies, and the KORA Augsburg team. Furthermore, we are grateful to Franziska Scharl (Helmholtz Center Munich) for advice regarding the genotyping. Finally, we are indebted to all study participants.

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Author notes

  1. C Holzapfel and H Grallert: These authors contributed equally to this work.

Authors and Affiliations

  1. Else Kröner-Fresenius-Center for Nutritional Medicine, Technische Universität München, Munich, Germany

    C Holzapfel & H Hauner

  2. Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

    C Holzapfel, H Grallert, C Huth, S Wahl, B Fischer, A Döring, I M Rückert, H-E Wichmann, T Illig & I M Heid

  3. Institute of Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilans-Universität and Klinikum Grosshadern, Munich, Germany

    H Grallert & H-E Wichmann

  4. Institute of Epidemiology and Preventive Medicine, Regensburg University Medical Center, Regensburg, Germany

    B Fischer & I M Heid

  5. Department of Child and Adolescent Psychiatry, LVR-Klinikum Essen, University of Duisburg-Essen, Essen, Germany

    A Hinney & J Hebebrand

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  1. C Holzapfel
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Holzapfel, C., Grallert, H., Huth, C. et al. Genes and lifestyle factors in obesity: results from 12 462 subjects from MONICA/KORA. Int J Obes 34, 1538–1545 (2010). https://doi.org/10.1038/ijo.2010.79

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