Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course

Mariaelisa Graff, Julius S. Ngwa, Tsegaselassie Workalemahu, Georg Homuth, Sabine Schipf, Alexander Teumer, Henry Völzke, Henri Wallaschofski, Goncalo R. Abecasis, Lakatta Edward, Cucca Francesco, Serena Sanna, Paul Scheet, David Schlessinger, Carlo Sidore, Xiangjun Xiao, Zhaoming Wang, Stephen J. Chanock, Kevin B. Jacobs, Richard B. HayesFrank Hu, Rob M. Van Dam, Richard J. Crout, Mary L. Marazita, John R. Shaffer, Larry D. Atwood, Caroline S. Fox, Nancy L. Heard-Costa, Charles White, Audrey C. Choh, Stefan A. Czerwinski, Ellen W. Demerath, Thomas D. Dyer, Bradford Towne, Najaf Amin, Ben A. Oostra, Cornelia M. Van Duijn, M. Carola Zillikens, Tönu Esko, Mari Nelis, Tit Nikopensius, Andres Metspalu, David P. Strachan, Keri Monda, Lu Qi, Kari E. North, L. Adrienne Cupples, Penny Gordon-Larsen, Sonja I. Berndt

Research output: Contribution to journalArticle

Abstract

Genetic loci forbodymassindex (BMI) in adolescenceandyoungadulthood, a period of high risk for weight gain, are understudied, yet may yield important insight into the etiology of obesity and early intervention. To identify novel genetic loci and examine the influence of known loci on BMI during this critical time period in late adolescence and early adulthood, we performed a two-stage meta-analysis using 14 genome-wide association studies in populations of European ancestry with data on BMI between ages 16 and 25 in up to 29 880 individuals. We identified seven independent loci (P < 5.0 × 10-8) near FTO (P = 3.72 × 10-23), TMEM18 (P = 3.24 × 10-17), MC4R (P = 4.41 × 10-11), TNNI3K (P = 4.32 × 10-9), SEC16B (P = 6.24 × 10-8), GNPDA2 (P = 1.11 × 10-8) and POMC (P = 4.94 × 1028) as well as a potential secondary signal at the POMC locus (rs2118404, P = 2.4 × 10-5 after conditioning on the established single-nucleotide polymorphism at this locus) in adolescents and young adults. To evaluate the impact of the established genetic loci on BMI at these young ages, we examined differences between the effect sizes of 32 published BMI loci in European adult populations (aged 18-90) and those observed in our adolescent and young adult meta-analysis. Four loci (near PRKD1, TNNI3K, SEC16B and CADM2) had larger effects and one locus (near SH2B1) had a smaller effect on BMI during adolescence and young adulthood compared with older adults (P < 0.05). These results suggest that genetic loci for BMI can vary in their effects across the life course, underlying the importance of evaluating BMI at different ages.

Original languageEnglish (US)
Pages (from-to)3597-3607
Number of pages11
JournalHuman molecular genetics
Volume22
Issue number17
DOIs
StatePublished - Sep 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Graff, M., Ngwa, J. S., Workalemahu, T., Homuth, G., Schipf, S., Teumer, A., Völzke, H., Wallaschofski, H., Abecasis, G. R., Edward, L., Francesco, C., Sanna, S., Scheet, P., Schlessinger, D., Sidore, C., Xiao, X., Wang, Z., Chanock, S. J., Jacobs, K. B., ... Berndt, S. I. (2013). Genome-wide analysis of BMI in adolescents and young adults reveals additional insight into the effects of genetic loci over the life course. Human molecular genetics, 22(17), 3597-3607. https://doi.org/10.1093/hmg/ddt205