Abstract 785: Is genetic ancestry associated with mortality risk after accounting for neighborhood socioeconomic status? A study of African American men

Background Genetic ancestry, a correlate of self-identified race/ethnicity, could be associated with mortality risk, allowing for more targeted treatments for cancer and other chronic diseases. However, associations may be confounded by neighborhood socioeconomic status (nSES). We investigated whether African ancestry and nSES were independently associated with all-cause mortality in a cohort of African American trial participants. Methods We constructed a cohort of American-born participants of African descent from the Prostate, Lung, Colorectal and Ovarian screening trial. Participants were enrolled from 1993-1998 and followed through 2019 or until death, whichever came first. Genetic ancestry (% African) was estimated using a principal components analysis of genome-wide SNP data and validated against European, African, and Asian panels. A nSES index was estimated using principal component analysis of census tract measures of income, housing, and employment. Census tract was assessed in 2012 for residences of living participants. Last known address was assigned to participants who died prior to 2012. We assigned 2000 census data to those who died prior to 2010, and assigned 2006-2010 American Community Survey data to those who were alive after 2010. Hazard ratios for associations between these variables and all-cause mortality were estimated using sequentially adjusted Cox proportional hazards models with sociodemographic, behavioral, and neighborhood contextual covariates. We tested whether mortality associations with ancestry varied by nSES using multiplicative interaction terms. All tests were two-sided with alpha=0.05. Results Among 2239 African American participants, there were 901 deaths over 40,767 person-years of follow-up. Mean baseline age was 61.7, 45% were men, and the mean percentage of African ancestry was 74.3. In unadjusted models, a 10% increase in African ancestry was associated with a 7% higher rate of all-cause mortality (HR: 1.07, 95% CI: 1.02, 1.12), but this attenuated to the null after adjusting for covariates (aHR: 1.01, 95% CI: 0.96, 1.06). Participants in nSES Q5 had 45% lower rate of mortality compared to those in Q1 in unadjusted models (HR: 0.55, 95% CI: 0.44, 0.68, Ptrend Discussion Our findings suggest that nSES is a stronger independent correlate of mortality than genetic ancestry, which was only weakly associated with mortality after accounting for other factors. Larger studies with wider variability in African ancestry and geographic context are needed to confirm these findings. Citation Format: Hari S. Iyer, Scarlett L. Gomez, Iona Cheng, Timothy R. Rebbeck. Is genetic ancestry associated with mortality risk after accounting for neighborhood socioeconomic status? A study of African American men [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 785.