7. PROJECT SUMMARYA large body of evidence indicates that high-quality social relationships are correlated with decreased risk formorbidity and mortality from a range of disease outcomes and that social disconnection and poor relationshipquality are correlated with considerable risk for negative health outcomes. Although most of the work in thisarea is correlational in nature it is often interpreted as if it is causal. Genetically informed research methodscan allow researchers to rule-out causal explanations for epidemiological associations and/or identify effectsthat may be consistent with a causal influence. Using co-twin control methods and a comprehensive new datacollection in the Washington State Twin Registry (WSTR) this grant brings together a diverse and establishedscientific team to examine a series of unanswered questions around social relationships health and cognitivefunctioning all of which center on causal inference. The work in this proposal is guided by three Specific Aimsthat will: (1) Conduct a detailed assessment of social relationship functioning in the WSTR and usethese variables in co-twin analyses of health and health behaviors. We will conduct a new data collectionon 1000 adult twin pairs (N = 2000) in the WSTR and complete a deep phenotyping of key relationshipquality variables including social integration relationship satisfaction/quality and attachment styles. UnderAim 1 we will also collect DNA methylation data and use a series of epigenetic clocks to characterizeaccelerated biological aging among our main study outcomes; (2) Conduct a detailed neuropsychologicalassessment of cognitive functioning in the WSTR cohort and use these variables as key outcomes inco-twin models. Social isolation and loneliness may hasten declines in cognitive functioning but are theseassociations consistent with a causal effect? We will conduct detailed neuropsychological assessments of the2000 WSTR participants using assessments that target cognitive outcomes shown to be associated withaccelerated cognitive decline mild cognitive impairment and biomarkers of Alzheimers disease and relateddementias; and (3) Examine the association between objective measures of daily social functioning andthe health and cognitive outcomes in the WSTR. The Electronically Activated Recorder (EAR) is asmartphone application that records ambient sounds in participants daily lives and provides a means ofassessing social behaviors beyond self-report alone. We will collect EAR data from a sub-sample of 140 adultMZ twin pairs discordant for marital status (N = 280) from the WSTR to determine if within twin-pair differencesin the objective indices of social integration are associated with the health health behavior and cognitiveoutcomes. Successful completion of the proposed research will help build a causal foundation for public healthintervention efforts around social relationships.