High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study

Olesya Ajnakina*, Diana Shamsutdinova, Theresa Wimberley, Søren Dalsgaard, Andrew Steptoe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)
31 Downloads (Pure)

Abstract

Background: Attention deficit hyperactivity disorder (ADHD) is a highly heritable, neurodevelopmental disorder known to associate with more than double the risk of death compared with people without ADHD. Because most research on ADHD has focused on children and adolescents, among whom death rates are relatively low, the impact of a high polygenic predisposition to ADHD on accelerating mortality risk in older adults is unknown. Thus, the aim of the study was to investigate if a high polygenetic predisposition to ADHD exacerbates the risk of all-cause mortality in older adults from the general population in the UK. 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 (PGS-ADHDsingle) and (2) chronic obstructive pulmonary disease and younger age of giving first birth, which were shown to have a strong genetic correlation with ADHD using the multi-trait analysis of genome-wide association summary statistics; this polygenic score was referred to as PGS-ADHDmulti-trait. All-cause mortality was ascertained from the National Health Service central register that captures all deaths occurring in the UK. Results: The sample comprised 7133 participants with a mean age of 64.7 years (SD = 9.5, range = 50–101); of these, 1778 (24.9%) died during a period of 11.2 years. PGS-ADHDsingle was associated with a greater risk of all-cause mortality (hazard ratio [HR] = 1.06, 95% CI = 1.02–1.12, p = 0.010); further analyses showed this relationship was significant in men (HR = 1.07, 95% CI = 1.00–1.14, p = 0.043). Risk of all-cause mortality increased by an approximate 11% for one standard deviation increase in PGS-ADHDmulti-trait (HR = 1.11, 95% CI = 1.06–1.16, p < 0.001). When the model was run separately for men and women, the association between PGS-ADHDmulti-trait and an increased risk of all-cause mortality was significant in men (HR = 1.10, 95% CI = 1.03–1.18, p = 0.003) and women (HR = 1.11, 95% CI = 1.04–1.19, p = 0.003). Conclusions: A high polygenetic predisposition to ADHD is a risk factor for all-cause mortality in older adults. This risk is better captured when incorporating genetic information from correlated traits.

Original languageEnglish
Article number62
JournalBMC Medicine
Volume20
Issue number1
Early online date23 Feb 2022
DOIs
Publication statusE-pub ahead of print - 23 Feb 2022

Keywords

  • Attention deficit hyperactivity disorder
  • Genome-wide association studies
  • Healthy ageing
  • Mortality
  • Polygenic predisposition

Fingerprint

Dive into the research topics of 'High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study'. Together they form a unique fingerprint.

Cite this