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.

Details

Title
Genome-wide association study reveals dynamic role of genetic variation in infant and early childhood growth
Author
Helgeland, Øyvind 1   VIAFID ORCID Logo  ; Vaudel, Marc 2   VIAFID ORCID Logo  ; Juliusson, Petur B 3   VIAFID ORCID Logo  ; Holmen, Oddgeir Lingaas 4 ; Juodakis, Julius 5   VIAFID ORCID Logo  ; Bacelis, Jonas 6   VIAFID ORCID Logo  ; Jacobsson, Bo 7   VIAFID ORCID Logo  ; Lindekleiv, Haakon 8 ; Hveem, Kristian 9 ; Lie, Rolv Terje 10 ; Knudsen, Gun Peggy 11 ; Stoltenberg, Camilla 12   VIAFID ORCID Logo  ; Magnus, Per 13 ; Sagen, Jørn V 14   VIAFID ORCID Logo  ; Molven, Anders 15 ; Johansson, Stefan 16   VIAFID ORCID Logo  ; Njølstad, Pål Rasmus 17   VIAFID ORCID Logo 

1  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Genetics and Bioinformatics, Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway 
2  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway 
3  Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics and Adolescents, Haukeland University Hospital, Bergen, Norway; Department of Health Registries, Norwegian Institute of Public Health, Bergen, Norway 
4  KG Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Research Center, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway 
5  Department of Gynecology and Obstetrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 
6  Department of Gynecology and Obstetrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Gynecology and Obstetrics, Sahlgrenska University Hospital, Gothenburg, Sweden 
7  Department of Genetics and Bioinformatics, Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway; Department of Gynecology and Obstetrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden 
8  Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway 
9  KG Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Research Center, Levanger, Norway 
10  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway 
11  Department of Genetics and Bioinformatics, Health Data and Digitalisation, Norwegian Institute of Public Health, Oslo, Norway 
12  Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway; Norwegian Institute of Public Health, Oslo, Norway 
13  Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway; Institute of Health and Society, Faculty of Medicine, University of Oslo, Oslo, Norway 
14  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway; Hormone Laboratory, Haukeland University Hospital, Bergen, Norway 
15  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Clinical Medicine, University of Bergen, Bergen, Norway; Department of Pathology, Haukeland University Hospital, Bergen, Norway 
16  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway 
17  KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Pediatrics and Adolescents, Haukeland University Hospital, Bergen, Norway 
Pages
1-10
Publication year
2019
Publication date
Oct 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12308-0
ProQuest document ID
2299754253
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.