Characterization of the genetic architecture of infant and early childhood body mass index

Øyvind Helgeland^#^{1

2}, Marc Vaudel^#¹, Pol Sole-Navais³, Christopher Flatley³, Julius Juodakis³, Jonas Bacelis³, Ingvild L Koløen^{1

4}, Gun Peggy Knudsen⁵, Bente B Johansson¹, Per Magnus⁶, Ted Reichborn Kjennerud^{7

8}, Petur B Juliusson^{9

10

11}, Camilla Stoltenberg⁵, Oddgeir L Holmen¹², Ole A Andreassen^{13

14}, Bo Jacobsson^{2

3}, Pål R Njølstad^{15

16}, Stefan Johansson^{17

18}

Affiliations

¹ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
² Department of Genetics and Bioinformatics, Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
³ Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
⁵ Norwegian Institute of Public Health, Oslo, Norway.
⁶ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁷ Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁸ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁹ Department of Health Registry Research and Development, National Institute of Public Health, Bergen, Norway.
¹⁰ Department of Clinical Science, University of Bergen, Bergen, Norway.
¹¹ Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway.
¹² HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
¹³ NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁴ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁵ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. pal.njolstad@uib.no.
¹⁶ Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway. pal.njolstad@uib.no.
¹⁷ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. stefan.johansson@uib.no.
¹⁸ Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway. stefan.johansson@uib.no.

^# Contributed equally.

PMID: 35315439
DOI: 10.1038/s42255-022-00549-1

Characterization of the genetic architecture of infant and early childhood body mass index

Øyvind Helgeland et al. Nat Metab. 2022 Mar.

. 2022 Mar;4(3):344-358.

doi: 10.1038/s42255-022-00549-1. Epub 2022 Mar 21.

Authors

Affiliations

¹ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
² Department of Genetics and Bioinformatics, Health Data and Digitalization, Norwegian Institute of Public Health, Oslo, Norway.
³ Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
⁵ Norwegian Institute of Public Health, Oslo, Norway.
⁶ Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway.
⁷ Department of Mental Disorders, Norwegian Institute of Public Health, Oslo, Norway.
⁸ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁹ Department of Health Registry Research and Development, National Institute of Public Health, Bergen, Norway.
¹⁰ Department of Clinical Science, University of Bergen, Bergen, Norway.
¹¹ Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway.
¹² HUNT Research Centre, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
¹³ NORMENT Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁴ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
¹⁵ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. pal.njolstad@uib.no.
¹⁶ Children and Youth Clinic, Haukeland University Hospital, Bergen, Norway. pal.njolstad@uib.no.
¹⁷ Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway. stefan.johansson@uib.no.
¹⁸ Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway. stefan.johansson@uib.no.

^# Contributed equally.

PMID: 35315439
DOI: 10.1038/s42255-022-00549-1

Erratum in

Author Correction: Characterization of the genetic architecture of infant and early childhood body mass index.
Helgeland Ø, Vaudel M, Sole-Navais P, Flatley C, Juodakis J, Bacelis J, Koløen IL, Knudsen GP, Johansson BB, Magnus P, Kjennerud TR, Juliusson PB, Stoltenberg C, Holmen OL, Andreassen OA, Jacobsson B, Njølstad PR, Johansson S. Helgeland Ø, et al. Nat Metab. 2024 Feb;6(2):378. doi: 10.1038/s42255-024-01004-z. Nat Metab. 2024. PMID: 38337098 No abstract available.

Abstract

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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Comment in

The dynamic genetic architecture of early childhood BMI.
Downie CG, North KE. Downie CG, et al. Nat Metab. 2022 Mar;4(3):308-309. doi: 10.1038/s42255-022-00546-4. Nat Metab. 2022. PMID: 35315438 Free PMC article. No abstract available.

References

1. Fraser, A. et al. Cohort Profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int. J. Epidemiol. 42, 97–110 (2013). - PubMed
1. Rolland-Cachera, M. F., Deheeger, M., Maillot, M. & Bellisle, F. Early adiposity rebound: causes and consequences for obesity in children and adults. Int. J. Obes. 30, S11–S17 (2006).
1. NCD Risk Factor Collaboration (NCD-RisC). Worldwide trends in body mass index, underweight, overweight, and obesity from 1975 to 2016: a pooled analysis of 2,416 population-based measurement studies in 128.9 million children, adolescents, and adults. Lancet 390, 2627–2642 (2017).
1. World Health Organization. Consideration of the evidence on childhood obesity for the Commission on Ending Childhood Obesity: report of the ad hoc working group on science and evidence for ending childhood obesity (WHO, Geneva, 2016) http://apps.who.int/iris/bitstream/10665/206549/1/9789241565332_eng.pdf?...
1. Singh, A. S., Mulder, C., Twisk, J. W. R., van Mechelen, W. & Chinapaw, M. J. M. Tracking of childhood overweight into adulthood: a systematic review of the literature. Obes. Rev. 9, 474–488 (2008). - PubMed

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Characterization of the genetic architecture of infant and early childhood body mass index

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Characterization of the genetic architecture of infant and early childhood body mass index

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