Loneliness and depression: bidirectional mendelian randomization analyses using data from three large genome-wide association studies.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
21 Sep 2023
21 Sep 2023
Historique:
received:
22
11
2022
accepted:
08
09
2023
revised:
06
09
2023
medline:
22
9
2023
pubmed:
22
9
2023
entrez:
22
9
2023
Statut:
aheadofprint
Résumé
Major depression (MD) is a serious psychiatric illness afflicting nearly 5% of the world's population. A large correlational literature suggests that loneliness is a prospective risk factor for MD; correlational assocations of this nature may be confounded for a variety of reasons. This report uses Mendelian Randomization (MR) to examine potentially causal associations between loneliness and MD. We report on analyses using summary statistics from three large genome wide association studies (GWAS). MR analyses were conducted using three independent sources of GWAS summary statistics. In the first set of analyses, we used available summary statistics from an extant GWAS of loneliness to predict MD risk. We used two sources of outcome data: the Psychiatric Genomics Consortium (PGC) meta-analysis of MD (PGC-MD; N = 142,646) and the Million Veteran Program (MVP-MD; N = 250,215). Finally, we reversed analyses using data from the MVP and PGC samples to identify risk variants for MD and used loneliness outcome data from UK Biobank. We find robust evidence for a bidirectional causal relationship between loneliness and MD, including between loneliness, depression cases status, and a continuous measure of depressive symptoms. The estimates remained significant across several sensitivity analyses, including models that account for horizontal pleiotropy. This paper provides the first genetically-informed evidence that reducing loneliness may play a causal role in decreasing risk for depressive illness, and these findings support efforts to reduce loneliness in order to prevent or ameliorate MD. Discussion focuses on the public health significance of these findings, especially in light of the SARS-CoV-2 pandemic.
Identifiants
pubmed: 37735503
doi: 10.1038/s41380-023-02259-w
pii: 10.1038/s41380-023-02259-w
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : U.S. Department of Health & Human Services | NIH | National Institute on Aging (U.S. National Institute on Aging)
ID : R01AG078361-01
Organisme : U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH)
ID : K08MH127413
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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