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

Authors :
Rødevand L
Bahrami S
Frei O
Lin A
Gani O
Shadrin A
Smeland OB
Connell KSO
Elvsåshagen T
Winterton A
Quintana DS
Hindley GFL
Werner MCF
Djurovic S
Dale AM
Lagerberg TV
Steen NE
Andreassen OA
Source :
Translational psychiatry [Transl Psychiatry] 2021 Jan 05; Vol. 11 (1), pp. 3. Date of Electronic Publication: 2021 Jan 05.
Publication Year :
2021

Abstract

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.

Details

Language :
English
ISSN :
2158-3188
Volume :
11
Issue :
1
Database :
MEDLINE
Journal :
Translational psychiatry
Publication Type :
Academic Journal
Accession number :
33414458
Full Text :
https://doi.org/10.1038/s41398-020-01142-4