Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan

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  • dc.contributor.author Vilar-Ribó, Laura
  • dc.contributor.author Cabana-Domínguez, Judit
  • dc.contributor.author Martorell, Lourdes
  • dc.contributor.author Ramos-Quiroga, Josep Antoni
  • dc.contributor.author Sanchez-Roige, Sandra
  • dc.contributor.author Palmer, Abraham A.
  • dc.contributor.author Vilella, Elisabet
  • dc.contributor.author Ribasés, Marta
  • dc.contributor.author Muntané, Gerard
  • dc.contributor.author Soler Artigas, María
  • dc.date.accessioned 2023-06-12T05:39:06Z
  • dc.date.available 2023-06-12T05:39:06Z
  • dc.date.issued 2023
  • dc.description.abstract There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality. We confirmed a negative genetic correlation between ADHD and parental lifespan (rg = −0.36, P = 1.41e−16). Nineteen independent loci were jointly associated with both ADHD and parental lifespan, with most of the alleles that increased the risk for ADHD being associated with shorter lifespan. Fifteen loci were novel for ADHD and two were already present in the original GWAS on parental lifespan. Mendelian randomization analyses pointed towards a negative causal effect of ADHD liability on lifespan (P = 1.54e−06; Beta = −0.07), although these results were not confirmed by all sensitivity analyses performed, and further evidence is required. The present study provides the first evidence of a common genetic background between ADHD and lifespan, which may play a role in the reported effect of ADHD on premature mortality risk. These results are consistent with previous epidemiological data describing reduced lifespan in mental disorders and support that ADHD is an important health condition that could negatively affect future life outcomes.
  • dc.description.sponsorship This work was supported by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, 2017SGR-00444 and 2017SGR-1461), the Instituto de Salud Carlos III (PI18/01788, P19/01224, PI20/00041, PI21/00612, PI22/00464, FI18/00285 to LVR and CP22/00128 to MSA), the Ministry of Science, Innovation and Universities (IJC2018-035346-I to MSA and RYC2021-031324-I to JCD); the European Regional Development Fund (ERDF), the European Union H2020 Programme (H2020/2014–2020) under grant agreements no. 728018 (Eat2beNICE), no. 848228 (DISCOvERIE) and no. 2020604 (TIMESPAN) and the ECNP Network ‘ADHD across the Lifespan’ and “la Marató de TV3” (202228-30 and 202228-31). SSR was supported by funds from the California Tobacco-Related Disease Research Program (TRDRP; Grant Number T29KT0526 and T32IR5226), and NIH/NIDA DP1DA054394. AAP was supported by NIH grant P50DA037844 and R01AA029688 and Tobacco-Related Disease Research Program Grant number: 28IR-0070.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Vilar-Ribó L, Cabana-Domínguez J, Martorell L, Ramos-Quiroga JA, Sanchez-Roige S, Palmer AA, et al. Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan. Neuropsychopharmacol. 2023 Jun;48(7):981-90. DOI: 10.1038/s41386-023-01555-x
  • dc.identifier.doi http://dx.doi.org/10.1038/s41386-023-01555-x
  • dc.identifier.issn 0893-133X
  • dc.identifier.uri http://hdl.handle.net/10230/57142
  • dc.language.iso eng
  • dc.publisher Springer
  • dc.relation.ispartof Neuropsychopharmacol. 2023 Jun;48(7):981-90
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/728018
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/848228
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/2020604
  • dc.rights This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Trastorn per dèficit d'atenció amb hiperactivitat
  • dc.subject.other Genètica humana
  • dc.subject.other Esperança de vida
  • dc.title Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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