A systematic analysis of the contribution of genetics to multimorbidity and comparisons with primary care data.

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Tác giả: Louise M Allan, Kate Boddy, Jack Bowden, Lucía A Carrasco-Ribelles, João Delgado, Frank Dudbridge, Leon Farmer, Chris Fox, Timothy M Frayling, Carlos Gallego-Moll, Sara M Khalid, Sally E Lamb, Xiaoran Liang, Mary Mancini, Jane A H Masoli, David Melzer, Ninon Mounier, Olivia Murrin, Luke C Pilling, Albert Roso-Llorach, Linus Tata, Jose M Valderas, Concepción Violán, Bethany Voller, Ruby M Woodward

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : EBioMedicine , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 701880

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 R INTERPRETATION: Most pairs of chronic conditions show evidence of shared genetics, and co-occurrence in primary care, suggesting shared mechanisms. The identified patterns of shared genetics, negative correlations and discordance between genetic and observational data provide a foundation for future multimorbidity research. FUNDING: UK Medical Research Council [MR/W014548/1].
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