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

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 a...

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Autores principales: Ajnakina, Olesya, Shamsutdinova, Diana, Wimberley, Theresa, Dalsgaard, Søren, Steptoe, Andrew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864906/
https://www.ncbi.nlm.nih.gov/pubmed/35193558
http://dx.doi.org/10.1186/s12916-022-02279-3
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author Ajnakina, Olesya
Shamsutdinova, Diana
Wimberley, Theresa
Dalsgaard, Søren
Steptoe, Andrew
author_facet Ajnakina, Olesya
Shamsutdinova, Diana
Wimberley, Theresa
Dalsgaard, Søren
Steptoe, Andrew
author_sort Ajnakina, Olesya
collection PubMed
description 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-ADHD(single)) 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-ADHD(multi-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-ADHD(single) 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-ADHD(multi-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-ADHD(multi-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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02279-3.
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spelling pubmed-88649062022-02-28 High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study Ajnakina, Olesya Shamsutdinova, Diana Wimberley, Theresa Dalsgaard, Søren Steptoe, Andrew BMC Med Research Article 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-ADHD(single)) 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-ADHD(multi-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-ADHD(single) 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-ADHD(multi-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-ADHD(multi-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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12916-022-02279-3. BioMed Central 2022-02-23 /pmc/articles/PMC8864906/ /pubmed/35193558 http://dx.doi.org/10.1186/s12916-022-02279-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Ajnakina, Olesya
Shamsutdinova, Diana
Wimberley, Theresa
Dalsgaard, Søren
Steptoe, Andrew
High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title_full High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title_fullStr High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title_full_unstemmed High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title_short High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
title_sort high polygenic predisposition for adhd and a greater risk of all-cause mortality: a large population-based longitudinal study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864906/
https://www.ncbi.nlm.nih.gov/pubmed/35193558
http://dx.doi.org/10.1186/s12916-022-02279-3
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