Separating the genetics of childhood and adult obesity: a validation study of genetic scores for body mass index in adolescence and adulthood in the HUNT Study

Maria Brandkvist, Johan Håkon Bjørngaard, Rønnaug Astri Ødegård, Bjørn Olav Åsvold, George Davey Smith, Ben Brumpton, Kristian Hveem, Tom G Richardson, Gunnhild Åberge Vie

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

From a life-course perspective, genetic and environmental factors driving childhood obesity may have a lasting influence on health later in life. However, how obesity trajectories vary throughout the life-course remains unknown. Recently, Richardson et al. created powerful early life and adult gene scores for BMI in a comprehensive attempt to separate childhood and adult obesity. The childhood score was derived using questionnaire-based data administered to adults aged 40-69 regarding their relative body size at age 10, making it prone to recall and misclassification bias. We therefore attempted to validate the childhood and adult scores using measured BMI data in adolescence and adulthood among 66 963 individuals from the HUNT Study in Norway from 1963 to 2019. The predictive performance of the childhood score was better in adolescence and early adulthood while the predictive performance of the adult score was better in adulthood. In the age group 12-15.9 years, the variance explained by the childhood polygenic risk score was 6.7% versus 2.4% for the adult polygenic risk score. In the age group 24-29.9 years, the variance explained by the adult PRS was 3.9% versus 3.6% for the childhood PRS. Our findings support that genetic factors driving BMI differ at young age and in adulthood. Within the framework of multivariable Mendelian randomization, the validated childhood gene score can now be used to determine the consequence of childhood obesity on later disease.

Original languageEnglish
JournalHuman Molecular Genetics
Early online date4 Dec 2020
DOIs
Publication statusE-pub ahead of print - 4 Dec 2020

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