The positive association of obesity variants with adulthood adiposity strengthens over an 80-year period: A gene-by-birth year interaction

Ellen W. Demerath, Audrey C. Choh, William Johnson, Joanne E. Curran, Miryoung Lee, Claire Bellis, Thomas D. Dyer, Stefan A. Czerwinski, John Blangero, Bradford Towne

    Research output: Contribution to journalArticle

    28 Scopus citations

    Abstract

    Objective: To test the hypothesis that the statistical effect of obesity-related genetic variants on adulthood adiposity traits depends on birth year. Methods: The study sample included 907 related, non-Hispanic White participants in the Fels Longitudinal Study, born between 1901 and 1986, and aged 25-64.99 years (474 females; 433 males) at the time of measurement. All had both genotype data from which a genetic risk score (GRS) composed of 32 well-replicated obesity-related common single nucleotide polymorphisms was created, and phenotype data [including body mass index (BMI), waist circumference, and the sum of four subcutaneous skinfolds]. Maximum likelihood-based variance components analysis was used to estimate trait heritabilities, main effects of GRS and birth year, GRS-by-birth year interaction, sex, and age. Results: Positive GRS-by-birth year interaction effects were found for BMI (p < 0.001), waist circumference (p = 0.007), and skinfold thickness (p < 0.007). For example, each one-allele increase in GRS was estimated to result in a 0.16 increase in BMI among males born in 1930 compared to a 0.47 increase among those born in 1970. Conclusions: These novel findings suggest the influence of common obesity susceptibility variants has increased during the obesity epidemic.

    Original languageEnglish (US)
    Pages (from-to)175-185
    Number of pages11
    JournalHuman Heredity
    Volume75
    DOIs
    StatePublished - Apr 18 2013

    Keywords

    • Adiposity
    • Body mass index
    • Gene
    • Gene-by-environment interaction
    • Genetic
    • Heritability
    • Interaction
    • Obesity
    • Risk score
    • Secular trend
    • Single nucleotide polymorphism
    • Waist circumference

    ASJC Scopus subject areas

    • Genetics
    • Genetics(clinical)

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    Demerath, E. W., Choh, A. C., Johnson, W., Curran, J. E., Lee, M., Bellis, C., Dyer, T. D., Czerwinski, S. A., Blangero, J., & Towne, B. (2013). The positive association of obesity variants with adulthood adiposity strengthens over an 80-year period: A gene-by-birth year interaction. Human Heredity, 75, 175-185. https://doi.org/10.1159/000351742