Cargando…

Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study

IMPORTANCE: Insomnia has been associated with altered inflammatory response as well as increased risk of infections and sepsis in observational studies. However, these studies are prone to bias, such as residual confounding. To further understand the potential causal association between insomnia and...

Descripción completa

Detalles Bibliográficos
Autores principales: Thorkildsen, Marianne S., Gustad, Lise T., Mohus, Randi M., Burgess, Stephen, Nilsen, Tom I. L., Damås, Jan K., Rogne, Tormod
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413214/
https://www.ncbi.nlm.nih.gov/pubmed/37556136
http://dx.doi.org/10.1001/jamapsychiatry.2023.2717
_version_ 1785087086760558592
author Thorkildsen, Marianne S.
Gustad, Lise T.
Mohus, Randi M.
Burgess, Stephen
Nilsen, Tom I. L.
Damås, Jan K.
Rogne, Tormod
author_facet Thorkildsen, Marianne S.
Gustad, Lise T.
Mohus, Randi M.
Burgess, Stephen
Nilsen, Tom I. L.
Damås, Jan K.
Rogne, Tormod
author_sort Thorkildsen, Marianne S.
collection PubMed
description IMPORTANCE: Insomnia has been associated with altered inflammatory response as well as increased risk of infections and sepsis in observational studies. However, these studies are prone to bias, such as residual confounding. To further understand the potential causal association between insomnia and sepsis risk, a 2-sample Mendelian randomization (MR) approach should be explored. OBJECTIVE: To evaluate whether genetically predicted insomnia is associated with risk of sepsis. DESIGN, SETTING, AND PARTICIPANTS: Two-sample MR was performed to estimate the association between genetically predicted insomnia and sepsis risk. Data were obtained from a genome-wide association study identifying 555 independent genetic variants (R(2) < 0.01) strongly associated with insomnia (P < 5 × 10(−8)). Sensitivity analyses were conducted to address bias due to pleiotropy and sample overlap, along with mediation analyses and sex-stratified analyses. The insomnia data set included 2.4 million individuals of European ancestry from the UK Biobank and 23andMe. For sepsis, 462 918 individuals of European ancestry from the UK Biobank were included. Data were extracted between February and December 2022 and analyzed between March 2022 and March 2023. EXPOSURE: Genetically predicted insomnia. MAIN OUTCOME AND MEASURE: Sepsis. RESULTS: There were 593 724 individuals with insomnia and 10 154 cases of sepsis. A doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.37 (95% CI, 1.19-1.57; P = 7.6 × 10(−6)) for sepsis. Sensitivity analyses supported this observation. One-third of the association between genetically predicted insomnia and risk of sepsis was mediated through a combination of cardiometabolic risk factors for sepsis (body mass index, type 2 diabetes, smoking, or cardiovascular disease; overall proportion, 35.2%; 95% CI, 5.1-76.9). The association between insomnia and sepsis was more pronounced among women compared with men (women: odds ratio, 1.44; 95% CI, 1.24-1.68; men: OR, 1.10; 95% CI, 0.86-1.40). CONCLUSIONS AND RELEVANCE: The concordance between these findings and previous observational studies supports that insomnia is potentially causally associated with the risk of sepsis. Thus, insomnia is a potential preventable risk factor of sepsis that should be further investigated, also in non-European populations.
format Online
Article
Text
id pubmed-10413214
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher American Medical Association
record_format MEDLINE/PubMed
spelling pubmed-104132142023-08-11 Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study Thorkildsen, Marianne S. Gustad, Lise T. Mohus, Randi M. Burgess, Stephen Nilsen, Tom I. L. Damås, Jan K. Rogne, Tormod JAMA Psychiatry Brief Report IMPORTANCE: Insomnia has been associated with altered inflammatory response as well as increased risk of infections and sepsis in observational studies. However, these studies are prone to bias, such as residual confounding. To further understand the potential causal association between insomnia and sepsis risk, a 2-sample Mendelian randomization (MR) approach should be explored. OBJECTIVE: To evaluate whether genetically predicted insomnia is associated with risk of sepsis. DESIGN, SETTING, AND PARTICIPANTS: Two-sample MR was performed to estimate the association between genetically predicted insomnia and sepsis risk. Data were obtained from a genome-wide association study identifying 555 independent genetic variants (R(2) < 0.01) strongly associated with insomnia (P < 5 × 10(−8)). Sensitivity analyses were conducted to address bias due to pleiotropy and sample overlap, along with mediation analyses and sex-stratified analyses. The insomnia data set included 2.4 million individuals of European ancestry from the UK Biobank and 23andMe. For sepsis, 462 918 individuals of European ancestry from the UK Biobank were included. Data were extracted between February and December 2022 and analyzed between March 2022 and March 2023. EXPOSURE: Genetically predicted insomnia. MAIN OUTCOME AND MEASURE: Sepsis. RESULTS: There were 593 724 individuals with insomnia and 10 154 cases of sepsis. A doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.37 (95% CI, 1.19-1.57; P = 7.6 × 10(−6)) for sepsis. Sensitivity analyses supported this observation. One-third of the association between genetically predicted insomnia and risk of sepsis was mediated through a combination of cardiometabolic risk factors for sepsis (body mass index, type 2 diabetes, smoking, or cardiovascular disease; overall proportion, 35.2%; 95% CI, 5.1-76.9). The association between insomnia and sepsis was more pronounced among women compared with men (women: odds ratio, 1.44; 95% CI, 1.24-1.68; men: OR, 1.10; 95% CI, 0.86-1.40). CONCLUSIONS AND RELEVANCE: The concordance between these findings and previous observational studies supports that insomnia is potentially causally associated with the risk of sepsis. Thus, insomnia is a potential preventable risk factor of sepsis that should be further investigated, also in non-European populations. American Medical Association 2023-10 2023-08-09 /pmc/articles/PMC10413214/ /pubmed/37556136 http://dx.doi.org/10.1001/jamapsychiatry.2023.2717 Text en Copyright 2023 Thorkildsen MS et al. JAMA Psychiatry. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Brief Report
Thorkildsen, Marianne S.
Gustad, Lise T.
Mohus, Randi M.
Burgess, Stephen
Nilsen, Tom I. L.
Damås, Jan K.
Rogne, Tormod
Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title_full Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title_fullStr Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title_full_unstemmed Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title_short Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study
title_sort association of genetically predicted insomnia with risk of sepsis: a mendelian randomization study
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10413214/
https://www.ncbi.nlm.nih.gov/pubmed/37556136
http://dx.doi.org/10.1001/jamapsychiatry.2023.2717
work_keys_str_mv AT thorkildsenmariannes associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT gustadliset associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT mohusrandim associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT burgessstephen associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT nilsentomil associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT damasjank associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy
AT rognetormod associationofgeneticallypredictedinsomniawithriskofsepsisamendelianrandomizationstudy