7. PROJECT SUMMARY A large body of evidence indicates that high-quality social relationships are correlated with decreased risk for morbidity and mortality from a range of disease outcomes, and that social disconnection and poor relationship quality are correlated with considerable risk for negative health outcomes. Although most of the work in this area is correlational in nature, it is often interpreted as if it is causal. Genetically informed research methods can allow researchers to rule-out causal explanations for epidemiological associations and/or identify effects that may be consistent with a causal influence. Using co-twin control methods and a comprehensive new data collection in the Washington State Twin Registry (WSTR), this grant brings together a diverse and established scientific team to examine a series of unanswered questions around social relationships, health, and cognitive functioning, all of which center on causal inference. The work in this proposal is guided by three Specific Aims that will: (1) Conduct a detailed assessment of social relationship functioning in the WSTR and use these variables in co-twin analyses of health and health behaviors. We will conduct a new data collection on 1,000 adult twin pairs (N = 2,000) in the WSTR and complete a “deep phenotyping” of key relationship quality variables, including social integration, relationship satisfaction/quality, and attachment styles. Under Aim 1, we will also collect DNA methylation data and use a series of epigenetic clocks to characterize accelerated biological aging among our main study outcomes; (2) Conduct a detailed neuropsychological assessment of cognitive functioning in the WSTR cohort and use these variables as key outcomes in co-twin models. Social isolation and loneliness may hasten declines in cognitive functioning, but are these associations consistent with a causal effect? We will conduct detailed neuropsychological assessments of the 2,000 WSTR participants using assessments that target cognitive outcomes shown to be associated with accelerated cognitive decline, mild cognitive impairment, and biomarkers of Alzheimer’s disease and related dementias; and (3) Examine the association between objective measures of daily social functioning and the health and cognitive outcomes in the WSTR. The Electronically Activated Recorder (EAR) is a smartphone application that records ambient sounds in participants’ daily lives and provides a means of assessing social behaviors beyond self-report alone. We will collect EAR data from a sub-sample of 140 adult MZ twin pairs discordant for marital status (N = 280) from the WSTR to determine if within twin-pair differences in the objective indices of social integration are associated with the health, health behavior, and cognitive outcomes. Successful completion of the proposed research will help build a causal foundation for public health intervention efforts around social relationships.

8. PROJECT NARRATIVE A large body of evidence indicates that high-quality social relationships are correlated with decreased risk for morbidity and mortality from a range of disease outcomes and that poor-quality relationships or social disconnection are correlated with considerable risk for negative health outcomes. Although most of the work in this area is correlational in nature, it is often interpreted as if it is causal. This grant uses a genetically informed research design to help build an empirical foundation for public health intervention efforts around social relationships, health, and cognitive functioning that is based on strong causal inference.