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

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Abstract

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.

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Acknowledgments

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.

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Authors and Affiliations

  1. Department of Psychology, University of California Riverside, 900 University Ave., Riverside, CA, 92521, USA

    Chandra A. Reynolds

  2. Department of Psychology, University of Southern California, Los Angeles, CA, 90089, USA

    Margaret Gatz & Nancy L. Pedersen

  3. Department of Medical Epidemiology and Biostatistics, Karolinska Institute, 17177, Stockholm, Sweden

    Margaret Gatz, Anna K. Dahl Aslan & Nancy L. Pedersen

  4. Epidemiology, Biostatistics and Bio-demography, Institute of Public Health, University of Southern Denmark, 5000, Odense C, Denmark

    Kaare Christensen, Lene Christiansen & Matt McGue

  5. Department of Clinical Genetics and Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Odense, Denmark

    Kaare Christensen

  6. Institute of Gerontology, School of Health and Welfare, Jönköping University, Jönköping, Sweden

    Anna K. Dahl Aslan

  7. Department of Public Health & Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, Finland

    Jaakko Kaprio

  8. Department of Public Health, University of Helsinki, 00014, Helsinki, Finland

    Tellervo Korhonen

  9. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, 70211, Kuopio, Finland

    Tellervo Korhonen

  10. Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA

    William S. Kremen

  11. Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA

    Robert Krueger & Matt McGue

  12. Department of Psychology, The Pennsylvania State University, University Park, PA, USA

    Jenae M. Neiderhiser

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  1. Chandra A. Reynolds
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for the IGEMS consortium

Corresponding author

Correspondence to Chandra A. Reynolds.

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Conflict of interest

Dr. Korhonen has served as a consultant on nicotine dependence for Pfizer (Finland) in 2011-2015.

Research involving Human Participants and/or Animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the respective institutional and/or national research committees for each participating study providing archival data, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants from their respective parent study.

Additional information

Members of the consortium on Interplay of Genes and Environment across Multiple Studies (IGEMS) are listed in Appendix.

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Supplementary material 1 (DOCX 153 kb)

Appendix

Appendix

Members of the consortium on Interplay of Genes and Environment across Multiple Studies (IGEMS) include: Nancy L. Pedersen (Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and Department of Psychology, University of Southern California, Los Angeles, CA), Kaare Christensen (Department of Epidemiology, University of Southern Denmark, Odense, Denmark), Anna K. Dahl Aslan (Institute of Gerontology, School of Health Sciences, Jönköping University, Jönköping, Sweden), Deborah Finkel (Department of Psychology, Indiana University Southeast, New Albany, IN), Carol E. Franz (Department of Psychiatry, University of California, San Diego, La Jolla, CA), Margaret Gatz (Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden, and Department of Psychology, University of Southern California, Los Angeles, CA), Briana N. Horwitz (Department of Psychology, California State University, Fullerton, CA), Boo Johansson (Department of Psychology, University of Gothenburg, Gothenburg, Sweden), Wendy Johnson (Department of Psychology and Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK), Jaakko Kaprio, Department of Public Health, University of Helsinki, Helsinki, Finland), William S. Kremen (Department of Psychiatry, University of California, San Diego, and VA Center of Excellence for Stress and Mental Health, La Jolla, CA), Robert Krueger (Department of Psychology, University of Minnesota, Minneapolis, MN), Michael J. Lyons (Department of Psychological and Brain Sciences, Boston University, Boston, MA), Matt McGue (Department of Psychology, University of Minnesota, Minneapolis, MN), Jenae M. Neiderhiser (Department of Psychology, The Pennsylvania State University, University Park, PA), Matthew S. Panizzon (Department of Psychiatry, University of California, San Diego, La Jolla, CA), Inge Petersen (Department of Epidemiology, University of Southern Denmark, Odense, Denmark), and Chandra A. Reynolds (Department of Psychology, University of California-Riverside, Riverside, CA).

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Reynolds, C.A., Gatz, M., Christensen, K. et al. Gene–Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood: Is APOE a Variability Gene?. Behav Genet 46, 4–19 (2016). https://doi.org/10.1007/s10519-015-9761-3

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