GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI.
Couto Alves A., De Silva NMG., Karhunen V., Sovio U., Das S., Taal HR., Warrington NM., Lewin AM., Kaakinen M., Cousminer DL., Thiering E., Timpson NJ., Bond TA., Lowry E., Brown CD., Estivill X., Lindi V., Bradfield JP., Geller F., Speed D., Coin LJM., Loh M., Barton SJ., Beilin LJ., Bisgaard H., Bønnelykke K., Alili R., Hatoum IJ., Schramm K., Cartwright R., Charles M-A., Salerno V., Clément K., Claringbould AAJ., BIOS Consortium None., van Duijn CM., Moltchanova E., Eriksson JG., Elks C., Feenstra B., Flexeder C., Franks S., Frayling TM., Freathy RM., Elliott P., Widén E., Hakonarson H., Hattersley AT., Rodriguez A., Banterle M., Heinrich J., Heude B., Holloway JW., Hofman A., Hyppönen E., Inskip H., Kaplan LM., Hedman AK., Läärä E., Prokisch H., Grallert H., Lakka TA., Lawlor DA., Melbye M., Ahluwalia TS., Marinelli M., Millwood IY., Palmer LJ., Pennell CE., Perry JR., Ring SM., Savolainen MJ., Rivadeneira F., Standl M., Sunyer J., Tiesler CMT., Uitterlinden AG., Schierding W., O'Sullivan JM., Prokopenko I., Herzig K-H., Smith GD., O'Reilly P., Felix JF., Buxton JL., Blakemore AIF., Ong KK., Jaddoe VWV., Grant SFA., Sebert S., McCarthy MI., Järvelin M-R., Early Growth Genetics (EGG) Consortium None.
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.