Journal
NATURE METABOLISM
Volume 4, Issue 3, Pages 344-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42255-022-00549-1
Keywords
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Categories
Funding
- Helse Vest's Open Research [912250, F-12144]
- Novo Nordisk Foundation [NNF19OC0057445, 54741]
- Research Council of Norway [315599, 240413]
- European Research Council (AdG SELECTionPREDISPOSED) [293574]
- Bergen Research Foundation
- Stiftelsen Kristian Gerhard Jebsen (Translational Medical Center)
- University of Bergen
- Western Norway Regional Health Authority (Strategic Fund Personalized Medicine for Children and Adults)
- Norwegian Diabetes Association
- Research Council of Norway through its Centres of Excellence funding scheme [262700, 223273]
- Better Health by Harvesting Biobanks [229624]
- Swedish Research Council, Stockholm, Sweden [2015-02559]
- Research Council of Norway (FRIMEDBIO) [547711, 273291]
- March of Dimes [21-FY16-121]
- Norwegian Ministry of Health and Care Services
- Ministry of Education and Research, National Institutes of Health (NIH)/NIEHS [N01-ES-75558]
- NIH/NINDS [UO1 NS 047537-01, UO1 NS 047537-06A1]
- UK Medical Research Council (MRC) [217065/Z/19/Z]
- Wellcome [217065/Z/19/Z]
- Wellcome Trust [076467/Z/05/Z]
- MRC [076467/Z/05/Z]
- 23andMe
- Swedish Research Council [2015-02559] Funding Source: Swedish Research Council
- European Research Council (ERC) [293574] Funding Source: European Research Council (ERC)
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This study characterizes genetic loci associated with early childhood body mass index, highlighting the roles of genes involved in monogenic obesity, appetite regulation, and energy expenditure. The study identifies 46 loci associated with early childhood body mass index at different ages and represents four major growth patterns. The findings provide insights into the genetic factors influencing early childhood growth and suggest potential treatment strategies.
Helgeland et al. characterize genetic loci associated with early childhood body mass index, highlighting roles of genes involved in monogenic obesity, appetite regulation and energy expenditure, many of which show age-specific association patterns. Early childhood obesity is a growing global concern; however, the role of common genetic variation on infant and child weight development is unclear. Here, we identify 46 loci associated with early childhood body mass index at specific ages, matching different child growth phases, and representing four major trajectory patterns. We perform genome-wide association studies across 12 time points from birth to 8 years in 28,681 children and their parents (27,088 mothers and 26,239 fathers) in the Norwegian Mother, Father and Child Cohort Study. Monogenic obesity genes are overrepresented near identified loci, and several complex association signals near LEPR, GLP1R, PCSK1 and KLF14 point towards a major influence for common variation affecting the leptin-melanocortin system in early life, providing a link to putative treatment strategies. We also demonstrate how different polygenic risk scores transition from birth to adult profiles through early child growth. In conclusion, our results offer a fine-grained characterization of a changing genetic landscape sustaining early childhood growth.
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