| Title: |
A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data |
| Authors: |
Murrin, O; Mounier, N; Voller, B; Tata, L; Gallego-Moll, C; Roso-Llorach, A; Carrasco-Ribelles, LA; Fox, C; Allan, LM; Woodward, RM; Liang, X; Valderas, JM; Khalid, S; Dudbridge, F; Lamb, SE; Mancini, M; Farmer, L; Boddy, K; Bowden, J; Melzer, D; Frayling, TM; Masoli, JAH; Pilling, LC; Violán, C; Delgado, J |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
Background: Multimorbidity, the presence of two or more conditions in one person, is common but studies are often limited to observational data and single datasets. We address this gap by integrating large-scale primary-care and genetic data from multiple studies to interrogate multimorbidity patterns and producing digital resources to support future research. Methods: We defined chronic, common, and heritable conditions in individuals aged ≥65 years, using two large primary-care databases [CPRD (UK) N = 2,425,014 and SIDIAP (Spain) N = 1,053,640], and estimated heritability using the same definitions in UK Biobank (N = 451,197). We used logistic regression to estimate the co-occurrence of pairs of conditions in the primary care data. Linkage disequilibrium score regression was used to estimate genetic similarity between pairs of conditions. Meta-analyses were conducted across databases, and up to three sources of genetic data, for each pair of conditions. We classified pairs of conditions as across or within-domain based on the international classification of disease. Findings: We identified 72 chronic conditions, with 43.6% of 2546 pairs showing higher co-occurrence than chance in primary care and evidence of shared genetics. Many across-domain pairs exhibited substantial shared genetics (e.g., iron deficiency anaemia and peripheral arterial disease: genetic correlation 𝑅𝑔 = 0.45 [95% Confidence Intervals 0.27:0.64]). 33 pairs displayed negative genetic correlations, such as skin cancer and rheumatoid arthritis (𝑅𝑔 = −0.14 [−0.21:−0.06]), due to potential adverse drug effects. Discordance between genetic and primary care data was also observed, e.g., abdominal aortic aneurysm and bladder cancer co-occurred in primary care but were not genetically correlated (Odds-Ratio = 2.23 [2.09:2.37], 𝑅𝑔 = 0.04 [−0.20:0.28]) and schizophrenia and fibromyalgia were less likely to co-occur together in primary care but were positively genetically correlated (OR = 0.84 [0.75:0.94], 𝑅𝑔 = 0.20 [0.11:0.29]). Interpretation: Most ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.1016/j.ebiom.2025.105584 |
| DOI: |
10.1016/j.ebiom.2025.105584 |
| Availability: |
https://doi.org/10.1016/j.ebiom.2025.105584; https://ora.ox.ac.uk/objects/uuid:ae625c24-bf7e-4095-8bc7-57489a95da97 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) |
| Accession Number: |
edsbas.96F5B70B |
| Database: |
BASE |