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 journalArticlepeer-review

31 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

Bibliographical note

Publisher Copyright:
© 2013 S. Karger AG, Basel.

Keywords

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

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