A framework for conducting GWAS using repeated measures data with an application to childhood BMI
Genetic effects on changes in human traits over time are understudied and may have important pathophysiological impact. We propose a framework that enables data quality control, implements mixed models to evaluate trajectories of change in traits, and estimates phenotypes to identify age-varying genetic effects in GWAS. Using childhood BMI as an example trait, we included 71,336 participants from six cohorts and estimated the slope and area under the BMI curve within four time periods (infancy, early childhood, late childhood and adolescence) for each participant, in addition to the age and BMI at the adiposity peak and the adiposity rebound. GWAS of the 12 estimated phenotypes identified 28 genome-wide significant variants at 13 loci, one of which (in DAOA) has not been previously associated with childhood or adult BMI. Genetic studies of changes in human traits over time could uncover unique biological mechanisms influencing quantitative traits.
Authors
- Sylvain P Sebert (ORCID: https://orcid.org/0000-0001-6681-6983)
- Zhanna Balkhiyarova (ORCID: https://orcid.org/0000-0003-3553-7126)
- Philippe Froguel (ORCID: https://orcid.org/0000-0003-2972-0784)
- Inga Prokopenko (ORCID: https://orcid.org/0000-0003-1624-7457)
- Nicole M. Warrington (ORCID: https://orcid.org/0000-0003-4195-775X)
- Yee-Ming Chan (ORCID: https://orcid.org/0000-0003-0554-8502)
- Kate M. Tilling (ORCID: https://orcid.org/0000-0002-1010-8926)
- Amélie Bonnefond (ORCID: https://orcid.org/0000-0001-9976-3005)
- Mickaël Canouil (ORCID: https://orcid.org/0000-0002-3396-4549)
- Alexessander Couto Alves (ORCID: https://orcid.org/0000-0001-8519-7356)
- Anni Heiskala (ORCID: https://orcid.org/0009-0009-2342-2488)
- Debbie A. Lawlor (ORCID: https://orcid.org/0000-0002-6793-2262)
- Marika Kaakinen (ORCID: https://orcid.org/0000-0002-9228-0462)
- Marjo‐Riitta Järvelin (ORCID: https://orcid.org/0000-0002-2149-0630)
- Struan F.A. Grant (ORCID: https://orcid.org/0000-0003-2025-5302)
- Kimberley Burrows (ORCID: https://orcid.org/0000-0002-3208-0389)
- Lijiao Ning (ORCID: https://orcid.org/0000-0001-5958-3253)
- Mathilde Boissel (ORCID: https://orcid.org/0000-0001-5719-8749)
- Håkon Håkonarson (ORCID: https://orcid.org/0000-0003-2814-7461)
- Jonathan P. Bradfield
Institutions
- Boston Children's Hospital (US)
- Centre National de la Recherche Scientifique (FR)
- Children's Hospital of Philadelphia (US)
- Harvard University (US)
- Inserm (FR)
- The University of Queensland (AU)
- Université de Lille (FR)
- Institut Pasteur de Lille (FR)
- University of Surrey (GB)
- University of Bristol (GB)
- MRC Epidemiology Unit (GB)
- Praevium Research (United States) (US)
- Imperial College London (GB)
- Brunel University of London (GB)
- Oulu University of Applied Sciences (FI)
- University of Pennsylvania (US)
- University of Oulu (FI)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-20
- DOI
- https://doi.org/10.1038/s41467-024-53687-3
- Citations
- 8
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 4.40
Funders
- British Heart Foundation
- Diabetes UK
- European Commission
- Horizon 2020 Framework Programme
- Medical Research Council
- National Health and Medical Research Council
- H2020 Science with and for Society