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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

BIOS Consortium, Early Growth Genetics EGG Conso, Alves, A. C., De Silva, N. M. G., Karhunen, V., Sovio, U., Das, S., Taal, H. R., Warrington, N. M., Lewin, A. M., Kaakinen, M., Cousminer, D. L., Thiering, E., Timpson, N. J., Bond, T. A., Lowry, E., Brown, C. D., Estivill, X., Lindi, V., Bradfield, J. P., Geller, F., Speed, D., Coin, L. J. M., Loh, M., Barton, S. J., Beilin, L. J., Bisgaard, H., Bonnelykke, K., Alili, R., Hatoum, I. J., Schramm, K., Cartwright, R., Charles, M-A., Salerno, V., Clement, K., Claringbould, A. A. J., van Duijn, C. M., Moltchanova, E., Eriksson, J. G., Elks, C., Feenstra, B., Flexeder, C., Franks, S., Frayling, T. M., Freathy, R. M., Elliott, P., Widen, E., Hakonarson, H., Hattersley, A. T., Rodriguez, A., Banterle, M. & Heinrich, J., 4-Sep-2019, In : Science Advances. 5, 9, 17 p., 3095.

Research output: Contribution to journalArticleAcademicpeer-review

  • BIOS Consortium
  • Early Growth Genetics EGG Conso
  • Alexessander Couto Alves
  • N. Maneka G. De Silva
  • Ville Karhunen
  • Ulla Sovio
  • Shikta Das
  • H. Rob Taal
  • Nicole M. Warrington
  • Alexandra M. Lewin
  • Marika Kaakinen
  • Diana L. Cousminer
  • Elisabeth Thiering
  • Nicholas J. Timpson
  • Tom A. Bond
  • Estelle Lowry
  • Christopher D. Brown
  • Xavier Estivill
  • Virpi Lindi
  • Jonathan P. Bradfield
  • Frank Geller
  • Doug Speed
  • Lachlan J. M. Coin
  • Marie Loh
  • Sheila J. Barton
  • Lawrence J. Beilin
  • Hans Bisgaard
  • Klaus Bonnelykke
  • Rohia Alili
  • Ida J. Hatoum
  • Katharina Schramm
  • Rufus Cartwright
  • Marie-Aline Charles
  • Vincenzo Salerno
  • Karine Clement
  • Annique A. J. Claringbould
  • Cornelia M. van Duijn
  • Elena Moltchanova
  • Johan G. Eriksson
  • Cathy Elks
  • Bjarke Feenstra
  • Claudia Flexeder
  • Stephen Franks
  • Timothy M. Frayling
  • Rachel M. Freathy
  • Paul Elliott
  • Elisabeth Widen
  • Hakon Hakonarson
  • Andrew T. Hattersley
  • Alina Rodriguez
  • Marco Banterle
  • Joachim Heinrich

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.

Original languageEnglish
Article number3095
Number of pages17
JournalScience Advances
Volume5
Issue number9
Publication statusPublished - 4-Sep-2019

    Keywords

  • BODY-MASS INDEX, GENOME-WIDE ASSOCIATION, BLOOD-PRESSURE, EARLY-LIFE, METABOLIC RISK, BIRTH COHORT, FTO GENE, ADIPOSITY, OBESITY, AGE

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