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Genetics and Epigenetics

BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort

International Journal of Obesity volumeĀ 41,Ā pages 759ā€“768 (2017)Cite this article

Subjects

Abstract

Objective:

The association of obesity susceptibility variants with change in body mass index (BMI) across the life course is not well understood.

Subjects:

In ancestry-stratified models of 5962 European American (EA), 2080 African American (AA) and 1582 Hispanic American (HA) individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health), we examined associations between 34 obesity single-nucleotide polymorphisms (SNPs) with per year change in BMI, measured by the slope from a growth-curve analysis of two or more BMI measurements between adolescence and young adulthood. For SNPs nominally associated with BMI change (P<0.05), we interrogated age differences within data collection Wave and time differences between age categories that overlapped between Waves.

Results:

We found SNPs in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 were significantly associated (P<0.0015ā‰ˆ0.05/34) with BMI change in EA and the ancestry-combined meta-analysis. rs9939609 in FTO met genome-wide significance at P<5eāˆ’08 in the EA and ancestry-combined analysis, respectively [Beta(se)=0.025(0.004);Beta(se)=0.021(0.003)]. No SNPs were significant after Bonferroni correction in AA or HA, although five SNPs in AA and four SNPs in HA were nominally significant (P<0.05). In EA and the ancestry-combined meta-analysis, rs3817334 near MTCH2 showed larger effects in younger respondents, whereas rs987237 near TFAP2B, showed larger effects in older respondents across all Waves. Differences in effect estimates across time for MTCH2 and TFAP2B are suggestive of either era or cohort effects.

Conclusion:

The observed association between variants in/near FTO, MC4R, MTCH2, TFAP2B, SEC16B and TMEM18 with change in BMI from adolescence to young adulthood suggest that the genetic effect of BMI loci varies over time in a complex manner, highlighting the importance of investigating loci influencing obesity risk across the life course.

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Acknowledgements

This study was funded by National Institutes of Health Grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development R01HD057194. The Carolina Population Center (R24 HD050924) provided general support. This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J Richard Udry, Peter S Bearman and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill and funded by Grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is given to Ronald R Rindfuss and Barbara Entwisle, of the University of North Carolina at Chapel Hill, for assistance in the original design. Information about how to obtain the Add Health data files is available at http://www.cpc.unc.edu/addhealth. No direct support was received from Grant P01-HD31921 for this analysis.

Author contributions

MG, KEN, EML and PG-L designed the study. MG, ASR and KLY contributed to data analysis. PG-L and KEN are responsible for data acquisition. MG, EML, KEN and PG-L drafted the manuscript. All the authors contributed to data interpretation and writing of the manuscript. MIG, KEN and PG-L had full access to the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All the authors have approved the final version of the manuscript.

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Authors and Affiliations

  1. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA

    M Graff,Ā K E North,Ā K L Young,Ā A L Mazul,Ā H M HighlandĀ &Ā K Mullan Harris

  2. Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, USA

    K E North,Ā K L Mohlke,Ā L A Lange,Ā E M LangeĀ &Ā K Mullan Harris

  3. RAND Corporation, Santa Monica, CA, USA

    A S Richardson

  4. Carolina Population Center, University of North Carolina, Chapel Hill, NC, USA

    K L YoungĀ &Ā P Gordon-Larsen

  5. Department of Genetics, University of North Carolina, Chapel Hill, NC, USA

    K L Mohlke,Ā L A LangeĀ &Ā E M Lange

  6. Department of Sociology, University of North Carolina, Chapel Hill, NC, USA

    K Mullan Harris

  7. Department of Nutrition, Gillings School of Global Public Health, School of Medicine, University of North Carolina, Chapel Hill, NC, USA

    P Gordon-Larsen

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  1. M Graff
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Correspondence to M Graff.

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Graff, M., North, K., Richardson, A. et al. BMI loci and longitudinal BMI from adolescence to young adulthood in an ethnically diverse cohort. Int J Obes 41, 759ā€“768 (2017). https://doi.org/10.1038/ijo.2016.233

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