Polygenic overlap and shared genetic loci between loneliness, severe mental disorders, and cardiovascular disease risk factors suggest shared molecular mechanisms.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
05 01 2021
Historique:
received: 10 06 2020
accepted: 04 12 2020
revised: 25 11 2020
entrez: 8 1 2021
pubmed: 9 1 2021
medline: 22 6 2021
Statut: epublish

Résumé

Clinical and epidemiological evidence suggest that loneliness is associated with severe mental disorders (SMDs) and increases the risk of cardiovascular disease (CVD). However, the mechanisms underlying the relationship between loneliness, SMDs, and CVD risk factors remain unknown. Here we explored overlapping genetic architecture and genetic loci shared between SMDs, loneliness, and CVD risk factors. We analyzed large independent genome-wide association study data on schizophrenia (SCZ), bipolar disorder (BD), major depression (MD), loneliness and CVD risk factors using bivariate causal mixture mode (MiXeR), which estimates the total amount of shared variants, and conditional false discovery rate to evaluate overlap in specific loci. We observed substantial genetic overlap between SMDs, loneliness and CVD risk factors, beyond genetic correlation. We identified 149 loci jointly associated with loneliness and SMDs (MD n = 67, SCZ n = 54, and BD n = 28), and 55 distinct loci jointly associated with loneliness and CVD risk factors. A total of 153 novel loneliness loci were found. Most of the shared loci possessed concordant effect directions, suggesting that genetic risk for loneliness may increase the risk of both SMDs and CVD. Functional analyses of the shared loci implicated biological processes related to the brain, metabolic processes, chromatin and immune system. Altogether, the study revealed polygenic overlap between loneliness, SMDs and CVD risk factors, providing new insights into their shared genetic architecture and common genetic mechanisms.

Identifiants

pubmed: 33414458
doi: 10.1038/s41398-020-01142-4
pii: 10.1038/s41398-020-01142-4
pmc: PMC7790035
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3

Subventions

Organisme : Norges Forskningsråd (Research Council of Norway)
ID : 223273, 262656, 248828
Pays : International

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Auteurs

Linn Rødevand (L)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. l.n.rodevand@medisin.uio.no.

Shahram Bahrami (S)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Oleksandr Frei (O)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Center for Bioinformatics, Department of Informatics, University of Oslo, 0316, Oslo, Norway.

Aihua Lin (A)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Osman Gani (O)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Alexey Shadrin (A)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Olav B Smeland (OB)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Kevin S O' Connell (KSO)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Torbjørn Elvsåshagen (T)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Neurology, Oslo University Hospital, Oslo, Norway.

Adriano Winterton (A)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Daniel S Quintana (DS)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Psychology, University of Oslo, Oslo, Norway.
KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway.

Guy F L Hindley (GFL)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Institute of Psychiatry, Psychology and Neuroscience, King's College London, 16 De Crespigny Park, London, SE5 8AB, UK.

Maren C F Werner (MCF)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Srdjan Djurovic (S)

Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
NORMENT Centre, Department of Clinical Science, University of Bergen, Bergen, Norway.

Anders M Dale (AM)

Department of Radiology, University of California San Diego, La Jolla, CA, 92093, USA.
Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, 92093, USA.
Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Department of Neurosciences, University of California San Diego, La Jolla, CA, 92093, USA.

Trine V Lagerberg (TV)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Nils Eiel Steen (NE)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Ole A Andreassen (OA)

NORMENT, Centre for Mental Disorders Research, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. ole.andreassen@medisin.uio.no.

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