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

Journal article
Authors 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
Pål Rasmus Njølstad
Published in Nature communications
Volume 10
Issue 1
Pages 4448
ISSN 2041-1723
Publication year 2019
Published at Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Pages 4448
Language en
Subject categories Obstetrics and gynaecology


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.

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