In this application, we propose a new collaboration among 7 existing longitudinal twin and family studies in Sweden, Denmark, and the US to lay the foundation for future studies of gene-environment interplay through harmonization of these data sets. The central focus is social data that can be related to outcomes in midlife and old age. The studies have a variety of measures relevant to 3 outcome domains: physical functioning and health, psychological well-being (emotional stability/depression), and cognitive health. The studies share a number of indicators of social environment from early childhood through adulthood (e.g. social context, early life experiences, SES). In all, we have data from 7105 twin pairs, age 24 to >90 at baseline, and up to 26 years of longitudinal follow-up. We propose to exploit the as yet unharnessed potential of these studies for considering questions about interplay between social context and late-life outcomes. The first steps will be to harmonize variables that measure outcomes and exposures (Yr 1) using tools such as DataSHaPer to identify overlapping item content and response formats, apply state-of- the-art psychometric analysis to establish measurement variance via IRT-factor approaches, and conduct meta analyses and integrated data analysis of pooled data as warranted. Using existing data, we will capitalize on advantages of the twin design for evaluating GXE and GE correlation, considering both genetic and environmental variance and measured genes and environments. After establishing that such relations exist, we will incorporate measures of inflammatory markers and/or genes (e.g. CRP and IL-6) in Swedish, Danish and American samples as a first concrete step to demonstrate added value of collaboration across these genetically informative twin materials (Yrs 3&4). Finally, we will explore other biological markers and/or genotypes) in relevant analyses of GXE and GE correlation (Yrs 4&5). Using harmonized data, longitudinal and cross-sectional analyses will evaluate conceptual models of gene- environment interplay in late-life functioning by testing the following hypotheses: That stable features of functioning: a) primarily reflect enduring influences of genetic factors, but b) are maintained in part through selection processes whereby high-functioning individuals create environments that reinforce their high functioning (GE correlation);that changes in functioning: a) primarily reflect the influences of environmental factors which b) are mediated in part by individual differences in physical, intellectual, and social activity, as shown by co-twin control methods;and that genetic influences on function in one area can be moderated by factors in other areas. This moderation can overwhelm genetic influences (as when physical disability impacts emotional or cognitive functioning by disrupting individuals'ability to control their environments). Alternatively, moderation can be by factors that trigger genetic vulnerabilities that might not otherwise be expressed (as when psychosocial stress triggers expression of genetic vulnerabilities to physical illness).

Public Health Relevance

Previous research has firmly established the association of social factors with late-life health and functioning. Yet this research does not explain the basis for these associations or how social effects interrelate with the biological and genetic factors known to contribute to late-life functioning. We will establish a consortium of seven longitudinal twin studies to explore the basis for the association of social factors and aging outcomes. The resulting analysis of the combined data from over 16,000 participants aims to understand why early life adversity, social factors such as isolation and loneliness are associated with diverse outcomes including mortality, and physical, emotional and cognitive health.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG037985-03
Application #
8318109
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M2))
Program Officer
King, Jonathan W
Project Start
2010-09-15
Project End
2015-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
3
Fiscal Year
2012
Total Cost
$639,370
Indirect Cost
$89,050
Name
University of Southern California
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Pedersen, Nancy L; Christensen, Kaare; Dahl, Anna K et al. (2013) IGEMS: the consortium on Interplay of Genes and Environment across Multiple Studies. Twin Res Hum Genet 16:481-9