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Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population.

ABSTRACT: Multimorbidity is an emerging topic in public health policy because of its increasing prevalence and socio-economic impact. However, the age- and gender-dependent trends of disease associations at fine resolution, and the underlying genetic factors, remain incompletely understood. Here, by analyzing disease networks from electronic medical records of primary health care, we identify key conditions and shared genetic factors influencing multimorbidity. Three types of diseases are outlined: "central", which include chronic and non-chronic conditions, have higher cumulative risks of disease associations; "community roots" have lower cumulative risks, but inform on continuing clustered disease associations with age; and "seeds of bursts", which most are chronic, reveal outbreaks of disease associations leading to multimorbidity. The diseases with a major impact on multimorbidity are caused by genes that occupy central positions in the network of human disease genes. Alteration of lipid metabolism connects breast cancer, diabetic neuropathy and nutritional anemia. Evaluation of key disease associations by a genome-wide association study identifies shared genetic factors and further supports causal commonalities between nervous system diseases and nutritional anemias. This study also reveals many shared genetic signals with other diseases. Collectively, our results depict novel population-based multimorbidity patterns, identify key diseases within them, and highlight pleiotropy influencing multimorbidity.

SUBMITTER: Amell A

PROVIDER: S-EPMC6206057 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population.

Amell A A Roso-Llorach A A Palomero L L Cuadras D D Galván-Femenía I I Serra-Musach J J Comellas F F de Cid R R Pujana M A MA Violán C C

Scientific reports 20181029 1

Multimorbidity is an emerging topic in public health policy because of its increasing prevalence and socio-economic impact. However, the age- and gender-dependent trends of disease associations at fine resolution, and the underlying genetic factors, remain incompletely understood. Here, by analyzing disease networks from electronic medical records of primary health care, we identify key conditions and shared genetic factors influencing multimorbidity. Three types of diseases are outlined: "centr ...[more]

PMID: 30374096

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Project description:BackgroundNetwork 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.MethodsA 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.ResultsRelative 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.ConclusionsMultimorbidity 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.

Project description:BACKGROUND:Non-communicable diseases (NCDs) are leading causes of premature disability and death worldwide. However, the lifetime risk of developing any NCD is unknown, as are the effects of shared common risk factors on this risk. METHODS AND FINDINGS:Between July 6, 1989, and January 1, 2012, we followed participants from the prospective Rotterdam Study aged 45 years and older who were free from NCDs at baseline for incident stroke, heart disease, diabetes, chronic respiratory disease, cancer, and neurodegenerative disease. We quantified occurrence/co-occurrence and remaining lifetime risk of any NCD in a competing risk framework. We additionally studied the lifetime risk of any NCD, age at onset, and overall life expectancy for strata of 3 shared risk factors at baseline: smoking, hypertension, and overweight. During 75,354 person-years of follow-up from a total of 9,061 participants (mean age 63.9 years, 60.1% women), 814 participants were diagnosed with stroke, 1,571 with heart disease, 625 with diabetes, 1,004 with chronic respiratory disease, 1,538 with cancer, and 1,065 with neurodegenerative disease. NCDs tended to co-occur substantially, with 1,563 participants (33.7% of those who developed any NCD) diagnosed with multiple diseases during follow-up. The lifetime risk of any NCD from the age of 45 years onwards was 94.0% (95% CI 92.9%-95.1%) for men and 92.8% (95% CI 91.8%-93.8%) for women. These risks remained high (>90.0%) even for those without the 3 risk factors of smoking, hypertension, and overweight. Absence of smoking, hypertension, and overweight was associated with a 9.0-year delay (95% CI 6.3-11.6) in the age at onset of any NCD. Furthermore, the overall life expectancy for participants without these risk factors was 6.0 years (95% CI 5.2-6.8) longer than for those with all 3 risk factors. Participants aged 45 years and older without the 3 risk factors of smoking, hypertension, and overweight at baseline spent 21.6% of their remaining lifetime with 1 or more NCDs, compared to 31.8% of their remaining life for participants with all of these risk factors at baseline. This difference corresponds to a 2-year compression of morbidity of NCDs. Limitations of this study include potential residual confounding, unmeasured changes in risk factor profiles during follow-up, and potentially limited generalisability to different healthcare settings and populations not of European descent. CONCLUSIONS:Our study suggests that in this western European community, 9 out of 10 individuals aged 45 years and older develop an NCD during their remaining lifetime. Among those individuals who develop an NCD, at least a third are subsequently diagnosed with multiple NCDs. Absence of 3 common shared risk factors is associated with compression of morbidity of NCDs. These findings underscore the importance of avoidance of these common shared risk factors to reduce the premature morbidity and mortality attributable to NCDs.

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Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population.

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Disease networks identify specific conditions and pleiotropy influencing multimorbidity in the general population.

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