GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.
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Shikta Das;
H Rob Taal;
Nicole M Warrington ;
Alexandra M Lewin ;
Marika Kaakinen ;
Diana L Cousminer ;
+83 more...
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 JM Coin ;
Marie Loh ;
Sheila J Barton ;
Lawrence J Beilin;
Hans Bisgaard;
Klaus Bønnelykke;
Rohia Alili ;
Ida J Hatoum;
Katharina Schramm ;
Rufus Cartwright;
Marie-Aline Charles ;
Vincenzo Salerno;
Karine Clément;
Annique AJ Claringbould ;
BIOS Consortium;
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 Widén ;
Hakon Hakonarson ;
Andrew T Hattersley;
Alina Rodriguez ;
Marco Banterle;
Joachim Heinrich;
Barbara Heude ;
John W Holloway ;
Albert Hofman ;
Elina Hyppönen ;
Hazel Inskip ;
Lee M Kaplan ;
Asa K Hedman;
Esa Läärä;
Holger Prokisch ;
Harald Grallert;
Timo A Lakka ;
Debbie A Lawlor;
Mads Melbye ;
Tarunveer S Ahluwalia ;
Marcella Marinelli ;
Iona Y Millwood;
Lyle J Palmer ;
Craig E Pennell ;
John R Perry ;
Susan M Ring ;
Markku J Savolainen ;
Fernando Rivadeneira ;
Marie Standl;
Jordi Sunyer ;
Carla MT Tiesler;
Andre G Uitterlinden;
William Schierding ;
Justin M O'Sullivan ;
Inga Prokopenko ;
Karl-Heinz Herzig;
George Davey Smith ;
Paul O'Reilly;
Janine F Felix ;
Jessica L Buxton;
Alexandra IF Blakemore;
Ken K Ong ;
Vincent WV Jaddoe ;
Struan FA Grant;
Sylvain Sebert ;
Mark I McCarthy ;
Marjo-Riitta Järvelin ;
Early Growth Genetics (EGG) Consortium;
(2019)
GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.
Science Advances, 5 (9).
eaaw3095-.
DOI: 10.1126/sciadv.aaw3095
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.
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