The effect of disease co-occurrence measurement on multimorbidity networks: a population-based study

Network analysis, a technique for describing relationships, can provide insights into patterns of co-occurring chronic health conditions. The effect that co-occurrence measurement has on disease network structure and resulting inferences has not been well studied. The purpose of the study was to compare structural differences among multimorbidity networks constructed using different co-occurrence measures.

A retrospective cohort study was conducted using four fiscal years of administrative health data (2015/16 - 2018/19) from the province of Manitoba, Canada (population 1.5 million). Chronic conditions were identified using diagnosis codes from electronic records of physician visits, surgeries, and inpatient hospitalizations, and grouped into categories using the Johns Hopkins Adjusted Clinical Group (ACG) System. Pairwise disease networks were separately constructed using each of seven co-occurrence measures: lift, relative risk, phi, Jaccard, cosine, Kulczynski, and joint prevalence. Centrality analysis was limited to the top 20 central nodes, with degree centrality used to identify potentially influential chronic conditions. Community detection was used to identify disease clusters. Similarities in community structure between networks was measured using the adjusted Rand index (ARI). Network edges were described using disease prevalence categorized as low (< 1%), moderate (1 to < 7%), and high (≥7%). Network complexity was measured using network density and frequencies of nodes and edges.

Relative risk and lift highlighted co-occurrences between pairs of low prevalence health conditions. Kulczynski emphasized relationships between high and low prevalence conditions. Joint prevalence focused on highly-prevalent conditions. Phi, Jaccard, and cosine emphasized associations involving moderately prevalent conditions. Co-occurrence measurement differences significantly affected the number and structure of identified disease clusters. When limiting the number of edges to produce visually interpretable graphs, networks had significant dissimilarity in the percentage of co-occurrence relationships in common, and in their selection of the highest-degree nodes.

Multimorbidity network analyses are sensitive to disease co-occurrence measurement. Co-occurrence measures should be selected considering their intrinsic properties, research objectives, and the health condition prevalence relationships of greatest interest. Researchers should consider conducting sensitivity analyses using different co-occurrence measures.