Gong, Jessica;
Preminger, Zohar;
Steptoe, Andrew;
Fancourt, Daisy;
(2025)
Protein signatures associated with loneliness and social isolation: Plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization.
Brain, Behavior, and Immunity
, 124
pp. 85-94.
10.1016/j.bbi.2024.11.024.
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Abstract
Introduction: The understanding of biological pathways related to loneliness and social isolation remains incomplete. Cutting-edge population-based proteomics offers opportunities to uncover novel biological pathways linked to social deficits. // Methods: This study employed a proteome-wide and data-driven approach to estimate the cross-sectional associations between objective measures of social connections (i.e., social isolation) and subjective measures (i.e., loneliness) with protein abundance, using the English Longitudinal Study of Ageing. // Results: Greater social isolation was associated with higher levels of 11 proteins (TNFRSF10A, MMP12, TRAIL-R2, SKR3, TNFRSF11A, VSIG2, PRSS8, FGFR2, KIM1, REN, and NEFL) after minimal adjustments; and three proteins were significantly associated after full adjustments (TNFRSF10A, TNFRSF11A, and HAOX1). Findings from two-sample Mendelian randomization indicated that a lower frequency of in-person social contact with friends or family causally increased levels of TNFRSF10A, TRAIL-R2, TNFRSF11A, and KIM1, and decreased the level of NEFL. The study also highlighted several enriched biological pathways, including necrosis and cell death regulation, dimerization of procaspase-8, and inhibition of caspase-8 pathways, which have previously not been linked to social deficits. // Conclusion: These findings could help explain the relationship between social deficits and disease, confirming the importance of continuing to explore novel biological pathways associated with social deficits.
| Type: | Article |
|---|---|
| Title: | Protein signatures associated with loneliness and social isolation: Plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.bbi.2024.11.024 |
| Publisher version: | http://dx.doi.org/10.1016/j.bbi.2024.11.024 |
| Language: | English |
| Additional information: | Copyright © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Social isolation; Loneliness; Proteomics; Mendelian randomization; Ageing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10200748 |
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