Plasma Metabolomic and Proteomic Profiling of the Mechanisms Underlying the Cumulative Impact of Co-occurring Psychiatric Disorders on Atopic Dermatitis
TL;DR
Psychiatric multimorbidity marks a sustained elevation in AD risk, potentially through overlapping inflammatory and metabolic pathways, potentially through overlapping inflammatory and metabolic pathways.
Abstract
Atopic dermatitis (AD) has been linked to psychiatric disorders, but the cumulative contribution of psychiatric multimorbidity to incident AD remains unclear. We integrated genome-wide association study summary statistics with UK Biobank cohort, metabolomic and proteomic data to evaluate genetic relationships, longitudinal associations and putative biological intermediates. High-definition likelihood and bidirectional GSMR assessed shared genetic architecture and directionality. Cox models, multimorbidity counts, weighted composite scores and stratified analyses assessed incident AD, including effect modification by serum vitamin D. Plasma metabolomic and proteomic data were examined using mediation analysis and proteome-wide Mendelian randomization. Genetic liability to 5 psychiatric traits was associated with higher AD risk, whereas reverse AD-to-psychiatric effects were not supported. Psychiatric disorders were prospectively associated with incident AD, with higher risk among participants with co-occurring disorders and higher weighted psychiatric burden. Vitamin D status modified these associations although causality cannot be inferred. A branched-chain amino acid metabolic pattern showed statistically significant but modest mediation (1.04%). Proteomic analyses prioritized HLA-DRA, MMP12, TNFRSF14, and VCAM1 as nonspecific inflammatory proteins associated with AD risk in psychiatric populations. Psychiatric multimorbidity marks a sustained elevation in AD risk, potentially through overlapping inflammatory and metabolic pathways.