Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?

Chandra A. Reynolds, Margaret Gatz, Kaare Christensen, Lene Christiansen, Anna K. Dahl Aslan, Jaakko Kaprio, Tellervo Korhonen, William S. Kremen, Robert Krueger, Matt McGue, Jenae M. Neiderhiser, Nancy L. Pedersen

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.
Original languageEnglish (US)
Pages (from-to)4-19
Number of pages16
JournalBehavior Genetics
Issue number1
StatePublished - Nov 4 2016

Bibliographical note

Funding Information:
IGEMS is supported by the National Institutes of Health Grant no. R01 AG037985. SATSA was supported by Grants R01 AG04563, R01 AG10175, the MacArthur Foundation Research Network on Successful Aging, the Swedish Council For Working Life and Social Research (FAS) (97:0147:1B, 2009-0795) and Swedish Research Council (825-2007-7460, 825-2009-6141). OCTO-Twin was supported by Grant R01 AG08861. Gender was supported by the MacArthur Foundation Research Network on Successful Aging, The Axel and Margaret Ax:son Johnson's Foundation, The Swedish Council for Social Research, and the Swedish Foundation for Health Care Sciences and Allergy Research. TOSS was supported by Grant R01 MH54610 from the National Institute of Health. The Danish Twin Registry is supported by Grants from The National Program for Research Infrastructure 2007 from the Danish Agency for Science and Innovation, the Velux Foundation and the US National Institute of Health (P01 AG08761). The Minnesota Twin Study of Adult Development and Aging was supported by NIA Grant R01 AG 06886. VETSA was supported by National Institute of Health Grants NIA R01 AG018384, R01 AG018386, R01 AG022381, and R01 AG022982, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the United States Department of Veterans Affairs has provided financial support for the development and maintenance of the Vietnam Era Twin (VET) Registry. This MIDUS study was supported by the John D. and Catherine T. MacArthur Foundation Research Network on Successful Midlife Development and by National Institute on Aging Grant AG20166. The Finnish Twin Cohort study has been supported by Academy of Finland Center of Excellence in Complex Disease Genetics (Grant numbers: 213506, 129680), the Academy of Finland (Grants 265240, 263278 & 264146 to JK) and ENGAGE ??? European Network for Genetic and Genomic Epidemiology, FP7-HEALTH-F4-2007, Grant agreement number 201413. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the NIA/NIH, or the VA.

Publisher Copyright:
© 2015, Springer Science+Business Media New York.


  • APOE
  • BMI
  • Cognitive performance
  • Depression
  • Gene–environment interaction
  • Twins
  • Variability gene


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