Background Attention deficit hyperactivity disorder (ADHD) is a highly heritable, neurodevelopmental disorder that is known to associate with a higher risk of all-mortality. Polygenetic predisposition to ADHD has been shown to be an important risk factor of all-cause mortality in older adults from the general population. However, it is not known if this risk is moderated by socio-economic markers (education and financial resources). A clearer understanding of this gene-by-environment interaction will help highlight potential pathways underlying the risk for all-cause mortality in older adults.

Methods Utilising data from the English Longitudinal Study of Ageing, which is an ongoing multidisciplinary study of the English population aged ≥50 years, polygenetic scores for ADHD were calculated using summary statistics for 1) ADHD diagnosis (PGS-ADHD_single), and 2) polygenic score encompassed common genetic markers associated with chronic obstructive pulmonary disease and younger age of giving first birth, which were shown to have a strong genetic correlation with ADHD by using genome-wide association summary statistics; this polygenic score was referred to as PGS-ADHD_multi-trait. All-cause mortality was ascertained from the National Health Service central register that captures all deaths occurring in the UK. Socioeconomic variables included educational attainment as measured with the number of years of completed schooling, and accumulated wealth.

Results The sample comprised 7106 individuals with the baseline mean age of 64.7 years (SD=9.5, range=50–101); 1772 (24.9%) died during the 11-year follow-up period. Independently from PGSs, one year of completed schooling decreased the risk for all-cause mortality by an average 4% (Hazard Ratio [HR]=0.96, 95%CI=0.95–0.98, p<0.001), whereas the moderate (HR=1.19, 95%CI=1.05–1.36, p=0.004) and low (HR=1.57, 95%CI=1.39–1.77, p<0.001) levels of accumulated wealth were associated with a higher risk for all-cause mortality during the follow-up period. 1-SD increase in PGS-ADHD_multi-trait was associated with an increase in risk for all-cause mortality by an average 10% (HR=1.10, 95%CI=1.10–1.21, p<0.005). However, the interaction effect between PGS-ADHD_single, and PGS-ADHD_multi-trait, and socio-economic markers was non-significant.

Conclusion A high polygenetic predisposition to ADHD as captured when incorporating genetic information from correlated traits, is a risk factor for all-cause mortality in older adults. Low education attainment and wealth are risk factors for all-mortality in older adults independently from the polygenic predisposition to ADHD. Therefore, providing psychoeducation about dealing with stress associated with having lower educational attainment and low accumulated wealth may prove beneficial in reducing risk for all-cause mortality in older adults.