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

Couto Alves, A; De Silva, NMG; Karhunen, V; Sovio, UORCID logo; Das, S; Taal, HR; Warrington, NMORCID logo; Lewin, AMORCID logo; Kaakinen, MORCID logo; Cousminer, DLORCID logo; +83 more...Thiering, E; Timpson, NJORCID logo; Bond, TA; Lowry, EORCID logo; Brown, CDORCID logo; Estivill, XORCID logo; Lindi, V; Bradfield, JP; Geller, FORCID logo; Speed, DORCID logo; Coin, LJORCID logo; Loh, MORCID logo; Barton, SJORCID logo; Beilin, LJ; Bisgaard, H; Bønnelykke, K; Alili, RORCID logo; Hatoum, IJ; Schramm, KORCID logo; Cartwright, R; Charles, MORCID logo; Salerno, V; Clément, K; Claringbould, AAORCID logo; BIOS Consortium; van Duijn, CMORCID logo; Moltchanova, E; Eriksson, JG; Elks, C; Feenstra, BORCID logo; Flexeder, C; Franks, S; Frayling, TMORCID logo; Freathy, RMORCID logo; Elliott, P; Widén, EORCID logo; Hakonarson, HORCID logo; Hattersley, AT; Rodriguez, AORCID logo; Banterle, M; Heinrich, J; Heude, BORCID logo; Holloway, JWORCID logo; Hofman, AORCID logo; Hyppönen, EORCID logo; Inskip, HORCID logo; Kaplan, LMORCID logo; Hedman, AK; Läärä, E; Prokisch, HORCID logo; Grallert, H; Lakka, TAORCID logo; Lawlor, DA; Melbye, MORCID logo; Ahluwalia, TSORCID logo; Marinelli, MORCID logo; Millwood, IY; Palmer, LJORCID logo; Pennell, CEORCID logo; Perry, JRORCID logo; Ring, SMORCID logo; Savolainen, MJORCID logo; Rivadeneira, FORCID logo; Standl, M; Sunyer, JORCID logo; Tiesler, CM; Uitterlinden, AG; Schierding, WORCID logo; O'Sullivan, JMORCID logo; Prokopenko, IORCID logo; Herzig, K; Smith, GDORCID logo; O'Reilly, P; Felix, JFORCID logo; Buxton, JL; Blakemore, AI; Ong, KKORCID logo; Jaddoe, VWORCID logo; Grant, SF; Sebert, SORCID logo; McCarthy, MIORCID logo; Järvelin, MORCID logo; Early Growth Genetics (EGG) Consortium and (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
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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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