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

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  1. Accounting for age of onset and family history improves power in genome-wide association studies

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  2. Early-Life Injuries and the Development of Attention-Deficit/Hyperactivity Disorder

    Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

  • Olesya Ajnakina
  • Diana Shamsutdinova
  • Theresa Wimberley
  • Søren Dalsgaard
  • Andrew Steptoe
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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.

OriginalsprogEngelsk
Artikelnummer62
TidsskriftB M C Medicine
Vol/bind20
ISSN1741-7015
DOI
StatusUdgivet - feb. 2022

ID: 78295416