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

Alexessander Couto Alves, Maneka De Silva, Ville Karhunen, Ulla Sovio, Shikta Das, H Rob Taal, Nicole M. Warrington, Alex Lewin, Marika Kaakinen, Diana L. Cousminer, Elisabeth Thiering, Nicholas Timpson, Tom A Bond, Estelle Lowry, Christopher Brown, Xavier Estivill, Virpi Lindi, Jonathan P Bradfield, Frank Geller, Doug SpeedLachlan J M Coin, Marie Loh, Sheila J Barton, Lawrence J Beilin, Hans Bisgaard, Klaus Bonnelykke, Rohia Alili, Ida Hatoum, Katharina Schramm, Rufus Cartwright, Marie-Aline Charles, Vincenzo Salerno, Karine Clement, Annique Claringbould, CM van Duijn, Elena Moltchanova, Timothy Frayling, Rachel Freathy, Debbie Lawlor, Susan Ring, George Davey Smith, Mark I McCarthy, Marjo-Riitta Järvelin, Early Growth Genetics (EGG) Consortium, BIOS Consortium

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Abstract

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 numbereaaw3095
Number of pages18
JournalAdvances in Medical Sciences
Volume5
Issue number9
DOIs
Publication statusPublished - 4 Sep 2019

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    Alves, A. C., De Silva, M., Karhunen, V., Sovio, U., Das, S., Taal, H. R., Warrington, N. M., Lewin, A., Kaakinen, M., Cousminer, D. L., Thiering, E., Timpson, N., Bond, T. A., Lowry, E., Brown, C., Estivill, X., Lindi, V., Bradfield, J. P., Geller, F., ... BIOS Consortium (2019). GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child and adult BMI. Advances in Medical Sciences, 5(9), [eaaw3095]. https://doi.org/10.1126/sciadv.aaw3095