A Comprehensive Evaluation of Life Purpose, Psychosocial Wellbeing, and Mortality
Creators: name: Alimujiang, Aliya
Publisher: name: My University
Year: 2022
Subjects: subject: Life purpose
subject: mortality
subject: genome-wide association study (GWAS)
subject: mediation analysis
subject: psychosocial wellbeing
subject: Public Health
subject: Health Sciences

description: Life purpose encompasses the meaning and direction a person has in life. A significant body literature has suggested that “purposeful living” is associated with better mental and physical health, but there are gaps in our understanding of these relationships. Life purpose, alongside many psychosocial constructs, has been studied for its effects on mortality, but comprehensive, well-designed studies are needed. Also, no previous analyses have explored the association between life purpose and cause-specific mortality. Moreover, psychosocial constructs are generally studied in isolation and their interconnectedness and shared biological pathways are ignored. Additionally, prior research has indicated that genetics are linked with life purpose, but no genome-wide association study (GWAS) on life purpose has previously been conducted. This dissertation aimed 1) to evaluate the association between life purpose and all-cause and cause-specific mortality; 2) to explore direct and indirect effects between psychosocial constructs and mortality; and 3) to identify genetic variants associated with life purpose. Aim one examined the association between life purpose and four-year all-cause and cause-specific mortality through the Cox-proportional hazard model among the Health and Retirement Study (HRS) participants. We found life purpose was statistically significantly associated with all-cause mortality (hazard ratio (HR)=2.43; 95%CI:1.57,3.75, comparing the lowest life purpose category with the highest category). Some significant cause-specific mortality associations with life purpose were also observed (heart conditions: HR=2.66; 95%CI:1.62,4.38). This work was published in JAMA Network Open in 2019. Aim two quantified the effect of a large set of psychosocial constructs on all-cause mortality and further evaluated whether behavioral or physical health status mediated the relationship. HRS collected data on 48 psychosocial constructs including life purpose. Latent class analysis was used to divide participants into mutually exclusive psychosocial wellbeing groups based on their pattern of psychosocial constructs. Psychosocial wellbeing group (good, average, and poor) was considered as the “exposure”, and physical health (functional status and comorbid conditions) and behavioral characteristics (physical activity, smoking, and alcohol) were mediators. We observed strong and statistically significant total effects for the association between survival time and psychosocial wellbeing (e.g., good versus poor survival rate (SR)=1.73; 95%CI:1.50,2.01). Through the mediation analysis, the direct effect via psychosocial wellbeing accounted for more than half of the total effect of this relationship (SR=1.46; 95%CI:1.27,1.67). However, indirect effects with individual mediators were also observed. In aim three, we conducted the first GWAS to identify genetic variants associated with life purpose in individuals of European ancestry (n=8,959) and African ancestry (n=1,641) using data from HRS. No SNPs achieved genome-wide significance (p&gt;5×10-8) in either ancestry group. We also performed a GWAS meta-analysis among European ancestry samples in HRS and Michigan Genomics Initiative Epidemiological Questionnaire Study using a single question on life purpose that overlapped between the two studies. The meta-analysis found no statistically significant SNP. Overall, the results of this dissertation add findings to our understanding of life purpose and psychosocial wellbeing. Aim one indicates that stronger life purpose was associated with decreased all-cause mortality. Aim two highlights the interconnectedness of psychosocial constructs, and shared indirect effects through physical and behavioral health factors between the association of psychosocial wellbeing and survival. Aim three serves as a stepping-stone to better understanding the genetic pathways that underpin life purpose. Future research should focus on evaluating the association of life purpose interventions with health outcomes, which could have major public health impacts.