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

Hum Hered. 2013;75(2-4):175-85. doi: 10.1159/000351742. Epub 2013 Sep 27.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity / genetics*
  • Adult
  • Body Mass Index
  • Female
  • Gene-Environment Interaction
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Models, Genetic
  • Obesity / genetics*
  • Parturition / genetics*
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics
  • Quantitative Trait, Heritable
  • Waist Circumference / genetics