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Phenotypically independent profiles relevant to mental health are genetically correlated

Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is...

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Autores principales: Roelfs, Daniel, Alnæs, Dag, Frei, Oleksandr, van der Meer, Dennis, Smeland, Olav B., Andreassen, Ole A., Westlye, Lars T., Kaufmann, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016894/
https://www.ncbi.nlm.nih.gov/pubmed/33795632
http://dx.doi.org/10.1038/s41398-021-01313-x
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author Roelfs, Daniel
Alnæs, Dag
Frei, Oleksandr
van der Meer, Dennis
Smeland, Olav B.
Andreassen, Ole A.
Westlye, Lars T.
Kaufmann, Tobias
author_facet Roelfs, Daniel
Alnæs, Dag
Frei, Oleksandr
van der Meer, Dennis
Smeland, Olav B.
Andreassen, Ole A.
Westlye, Lars T.
Kaufmann, Tobias
author_sort Roelfs, Daniel
collection PubMed
description Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into 13 distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White British ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, or psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlap with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders.
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spelling pubmed-80168942021-04-16 Phenotypically independent profiles relevant to mental health are genetically correlated Roelfs, Daniel Alnæs, Dag Frei, Oleksandr van der Meer, Dennis Smeland, Olav B. Andreassen, Ole A. Westlye, Lars T. Kaufmann, Tobias Transl Psychiatry Article Genome-wide association studies (GWAS) and family-based studies have revealed partly overlapping genetic architectures between various psychiatric disorders. Given clinical overlap between disorders, our knowledge of the genetic architectures underlying specific symptom profiles and risk factors is limited. Here, we aimed to derive distinct profiles relevant to mental health in healthy individuals and to study how these genetically relate to each other and to common psychiatric disorders. Using independent component analysis, we decomposed self-report mental health questionnaires from 136,678 healthy individuals of the UK Biobank, excluding data from individuals with a diagnosed neurological or psychiatric disorder, into 13 distinct profiles relevant to mental health, capturing different symptoms as well as social and risk factors underlying reduced mental health. Utilizing genotypes from 117,611 of those individuals with White British ancestry, we performed GWAS for each mental health profile and assessed genetic correlations between these profiles, and between the profiles and common psychiatric disorders and cognitive traits. We found that mental health profiles were genetically correlated with a wide range of psychiatric disorders and cognitive traits, with strongest effects typically observed between a given mental health profile and a disorder for which the profile is common (e.g. depression symptoms and major depressive disorder, or psychosis and schizophrenia). Strikingly, although the profiles were phenotypically uncorrelated, many of them were genetically correlated with each other. This study provides evidence that statistically independent mental health profiles partly share genetic underpinnings and show genetic overlap with psychiatric disorders, suggesting that shared genetics across psychiatric disorders cannot be exclusively attributed to the known overlapping symptomatology between the disorders. Nature Publishing Group UK 2021-04-01 /pmc/articles/PMC8016894/ /pubmed/33795632 http://dx.doi.org/10.1038/s41398-021-01313-x Text en © The Author(s) 2021 Open Access 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/.
spellingShingle Article
Roelfs, Daniel
Alnæs, Dag
Frei, Oleksandr
van der Meer, Dennis
Smeland, Olav B.
Andreassen, Ole A.
Westlye, Lars T.
Kaufmann, Tobias
Phenotypically independent profiles relevant to mental health are genetically correlated
title Phenotypically independent profiles relevant to mental health are genetically correlated
title_full Phenotypically independent profiles relevant to mental health are genetically correlated
title_fullStr Phenotypically independent profiles relevant to mental health are genetically correlated
title_full_unstemmed Phenotypically independent profiles relevant to mental health are genetically correlated
title_short Phenotypically independent profiles relevant to mental health are genetically correlated
title_sort phenotypically independent profiles relevant to mental health are genetically correlated
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016894/
https://www.ncbi.nlm.nih.gov/pubmed/33795632
http://dx.doi.org/10.1038/s41398-021-01313-x
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