eprintid: 10200748 rev_number: 9 eprint_status: archive userid: 699 dir: disk0/10/20/07/48 datestamp: 2024-11-27 12:10:49 lastmod: 2024-11-27 12:10:49 status_changed: 2024-11-27 12:10:49 type: article metadata_visibility: show sword_depositor: 699 creators_name: Gong, Jessica creators_name: Preminger, Zohar creators_name: Steptoe, Andrew creators_name: Fancourt, Daisy 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 ispublished: pub divisions: UCL divisions: B02 divisions: D12 divisions: G19 keywords: Social isolation; Loneliness; Proteomics; Mendelian randomization; Ageing note: 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/). 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. date: 2025-02 date_type: published publisher: Elsevier BV official_url: http://dx.doi.org/10.1016/j.bbi.2024.11.024 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2338921 doi: 10.1016/j.bbi.2024.11.024 lyricists_name: Gong, Jessica lyricists_id: JGONA20 actors_name: Gong, Jessica actors_id: JGONA20 actors_role: owner full_text_status: public publication: Brain, Behavior, and Immunity volume: 124 pagerange: 85-94 issn: 0889-1591 citation: 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 <https://doi.org/10.1016/j.bbi.2024.11.024>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10200748/1/Gong_1-s2.0-S0889159124007062-main.pdf