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Obesity is a heritable disease, characterised by excess adiposity that is measured by body mass index (BMI). While over 1,000 genetic loci are associated with BMI, less is known about the genetic contribution to adiposity trajectories over adulthood. We derive adiposity-change phenotypes from 24.5 million primary-care health records in over 740,000 individuals in the UK Biobank, Million Veteran Program USA, and Estonian Biobank, to discover and validate the genetic architecture of adiposity trajectories. Using multiple BMI measurements over time increases power to identify genetic factors affecting baseline BMI by 14%. In the largest reported genome-wide study of adiposity-change in adulthood, we identify novel associations with BMI-change at six independent loci, including rs429358 (APOE missense variant). The SNP-based heritability of BMI-change (1.98%) is 9-fold lower than that of BMI. The modest genetic correlation between BMI-change and BMI (45.2%) indicates that genetic studies of longitudinal trajectories could uncover novel biology of quantitative traits in adulthood.

Original publication

DOI

10.1038/s41467-024-49998-0

Type

Journal article

Journal

Nature communications

Publication Date

07/2024

Volume

15

Addresses

Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK. samvida@well.ox.ac.uk.

Keywords

Million Veteran Program, Estonian Biobank Research Team, Humans, Obesity, Genetic Predisposition to Disease, Body Mass Index, Phenotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, United States, Estonia, Female, Male, Adiposity, Genome-Wide Association Study, Electronic Health Records, United Kingdom