Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth

Øyvind Helgeland, Marc Vaudel, Petur B. Juliusson, Oddgeir Lingaas Holmen, Julius Juodakis, Jonas Bacelis, Bo Jacobsson, Haakon Lindekleiv, Kristian Hveem, Rolv Terje Lie, Gun Peggy Knudsen, Camilla Stoltenberg, Per Magnus, Jørn V. Sagen, Anders Molven, Stefan Johansson () and Pål Rasmus Njølstad ()
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Øyvind Helgeland: University of Bergen
Marc Vaudel: University of Bergen
Petur B. Juliusson: University of Bergen
Oddgeir Lingaas Holmen: Norwegian University of Science and Technology
Julius Juodakis: University of Gothenburg
Jonas Bacelis: University of Gothenburg
Bo Jacobsson: Norwegian Institute of Public Health
Haakon Lindekleiv: Department of Community Medicine, UiT The Arctic University of Norway
Kristian Hveem: Norwegian University of Science and Technology
Rolv Terje Lie: University of Bergen
Gun Peggy Knudsen: Norwegian Institute of Public Health
Camilla Stoltenberg: University of Bergen
Per Magnus: Norwegian Institute of Public Health
Jørn V. Sagen: University of Bergen
Anders Molven: University of Bergen
Stefan Johansson: University of Bergen
Pål Rasmus Njølstad: University of Bergen

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Infant and childhood growth are dynamic processes with large changes in BMI during development. By performing genome-wide association studies of BMI at 12 time points from birth to eight years (9286 children, 74,105 measurements) in the Norwegian Mother, Father, and Child Cohort Study, replicated in 5235 children, we identify a transient effect in the leptin receptor (LEPR) locus: no effect at birth, increasing effect in infancy, peaking at 6–12 months (rs2767486, P6m = 2.0 × 10−21, β6m = 0.16 sd-BMI), and little effect after age five. We identify a similar transient effect near the leptin gene (LEP), peaking at 1.5 years (rs10487505, P1.5y = 1.3 × 10−8, β1.5y = 0.079 sd-BMI). Both signals are protein quantitative trait loci for soluble-LEPR and LEP in plasma in adults independent from adult traits mapped to the respective genes, suggesting key roles of common variation in the leptin signaling pathway for healthy infant growth.

Date: 2019
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DOI: 10.1038/s41467-019-12308-0

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