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Abstract Background Mortality research has identified biomarkers predictive of all-cause mortality risk. Most of these markers, such as body mass index, are predictive cross-sectionally, while for others the longitudinal change has been shown to be predictive, for instance greater-than-average muscle and weight loss in older adults. And while sometimes markers are derived from imaging modalities such as DXA, full scans are rarely used. This study builds on that knowledge and tests two hypotheses to improve all-cause mortality prediction. The first hypothesis is that features derived from raw total-body DXA imaging using deep learning are predictive of all-cause mortality with and without clinical risk factors, meanwhile, the second hypothesis states that sequential total-body DXA scans and recurrent neural network models outperform comparable models using only one observation with and without clinical risk factors. Methods Multiple deep neural network architectures were designed to test theses hypotheses. The models were trained and evaluated on data from the 16-year-long Health, Aging, and Body Composition Study including over 15,000 scans from over 3000 older, multi-race male and female adults. This study further used explainable AI techniques to interpret the predictions and evaluate the contribution of different inputs. Results The results demonstrate that longitudinal total-body DXA scans are predictive of all-cause mortality and improve performance of traditional mortality prediction models. On a held-out test set, the strongest model achieves an area under the receiver operator characteristic curve of 0.79. Conclusion This study demonstrates the efficacy of deep learning for the analysis of DXA medical imaging in a cross-sectional and longitudinal setting. By analyzing the trained deep learning models, this work also sheds light on what constitutes healthy aging in a diverse cohort. 

Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10 -8 ) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10 -8 ) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89–1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO , and rs79967607 is in intron 1 of EPM2A . PLUTO , a lncRNA , regulates transcription of an adjacent gene, PDX1 , that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.