Conditional Disease Development extracted from Longitudinal Health Care Cohort Data using Layered Network Construction

Health care data holds great promise to be used in clinical decision support systems. However, frequent near-synonymous diagnoses recorded separately, as well as the sheer magnitude and complexity of the disease data makes it challenging to extract non-trivial conclusions beyond confirmatory associations from such a web of interactions. Here we present a systematic methodology to derive statistically valid conditional development of diseases. To this end we utilize a cohort of 5,512,469 individuals followed over 13 years at inpatient care, including data on disability pension and cause of death. By introducing a causal information fraction measure and taking advantage of the composite structure in the ICD codes, we extract an effective directed lower dimensional network representation (100 nodes and 130 edges) of our cohort. Unpacking composite nodes into bipartite graphs retrieves, for example, that individuals with behavioral disorders are more likely to be followed by prescription drug poisoning episodes, whereas women with leiomyoma were more likely to subsequently experience endometriosis. The conditional disease development represent putative causal relations, indicating possible novel clinical relationships and pathophysiological associations that have not been explored yet.

[1]  F. Roudot-thoraval,et al.  Gastroduodenal Ulcer and Erosions Are Related to Portal Hypertensive Gastropathy and Recent Alcohol Intake in Cirrhotic Patients , 2003, Digestive Diseases and Sciences.

[2]  J. Slansky,et al.  Multiple associations between a broad spectrum of autoimmune diseases, chronic inflammatory diseases and cancer. , 2012, Anticancer research.

[3]  E. Mittendorfer-Rutz,et al.  Associations between number of sick-leave days and future all-cause and cause-specific mortality: a population-based cohort study , 2014, BMC Public Health.

[4]  J. Olsen,et al.  Pernicious anaemia and cancer risk in Denmark. , 1996, British Journal of Cancer.

[5]  K. Byth,et al.  Smoking, alcohol, analgesics, and chronic duodenal ulcer. A controlled study of habits before first symptoms and before diagnosis. , 1984, Scandinavian journal of gastroenterology.

[6]  E. L. D. Melo,et al.  Anormalidades del sistema nervioso central y alteraciones de los miembros superiores en pacientes con mielomeningocele , 2008 .

[7]  A. Barabasi,et al.  Network medicine : a network-based approach to human disease , 2010 .

[8]  A. Barabasi,et al.  Human symptoms–disease network , 2014, Nature Communications.

[9]  Matthieu Latapy,et al.  Computing Communities in Large Networks Using Random Walks , 2004, J. Graph Algorithms Appl..

[10]  S. P. Chou,et al.  An examination of the alcohol consumption and peptic ulcer association--results of a national survey. , 1994, Alcoholism, clinical and experimental research.

[11]  J A Knottnerus,et al.  Multimorbidity in general practice: prevalence, incidence, and determinants of co-occurring chronic and recurrent diseases. , 1998, Journal of clinical epidemiology.

[12]  Yongli Xi,et al.  Increasing deaths from opioid analgesics in the United States , 2006, Pharmacoepidemiology and drug safety.

[13]  L. Jacobsson,et al.  Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists , 2005, Annals of the rheumatic diseases.

[14]  S. Haffner,et al.  Liver enzymes, the metabolic syndrome, and incident diabetes: the Mexico City diabetes study. , 2005, Diabetes care.

[15]  E. Pukkala,et al.  Elevated incidence of hematologic malignancies in patients with Sjögren's syndrome compared with patients with rheumatoid arthritis (Finland) , 1997, Cancer Causes & Control.

[16]  L. Larocca,et al.  Anemia in Hodgkin's lymphoma: the role of interleukin-6 and hepcidin. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  G. Silverberg Normal pressure hydrocephalus (NPH): ischaemia, CSF stagnation or both. , 2004, Brain : a journal of neurology.

[18]  Marylyn D. Ritchie,et al.  The foundation of precision medicine: integration of electronic health records with genomics through basic, clinical, and translational research , 2015, Front. Genet..

[19]  D. Gladman,et al.  Breast Cancer in Systemic Lupus Erythematosus , 2013, Oncology.

[20]  J. Pankow,et al.  Blood Viscosity and Hematocrit as Risk Factors for Type 2 Diabetes Mellitus The Atherosclerosis Risk in Communities ( ARIC ) Study , 2008 .

[21]  Darcy A. Davis,et al.  Exploring and Exploiting Disease Interactions from Multi-Relational Gene and Phenotype Networks , 2011, PloS one.

[22]  M. DePamphilis,et al.  HUMAN DISEASE , 1957, The Ulster Medical Journal.

[23]  Pablo Villoslada,et al.  Modules, networks and systems medicine for understanding disease and aiding diagnosis , 2014, Genome Medicine.

[24]  M. Mayes,et al.  Risk of malignancy in scleroderma: a population-based cohort study. , 2005, Arthritis and rheumatism.

[25]  Albert-László Barabási,et al.  A Dynamic Network Approach for the Study of Human Phenotypes , 2009, PLoS Comput. Biol..

[26]  S. Thurner,et al.  Spreading of diseases through comorbidity networks across life and gender , 2014, 1405.3801.

[27]  S. Brunak,et al.  Mining electronic health records: towards better research applications and clinical care , 2012, Nature Reviews Genetics.

[28]  C. Bogardus,et al.  High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. , 2002, Diabetes.

[29]  E. Schadt Molecular networks as sensors and drivers of common human diseases , 2009, Nature.

[30]  R. Winkelmann,et al.  Cancer and scleroderma. , 1979, Archives of dermatology.

[31]  G. Salles,et al.  Frequency and significance of anemia in non-Hodgkin's lymphoma patients. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  A. Barabasi,et al.  The human disease network , 2007, Proceedings of the National Academy of Sciences.

[33]  Tudor I. Oprea,et al.  Temporal disease trajectories condensed from population-wide registry data covering 6.2 million patients , 2014, Nature Communications.

[34]  G. Sharp,et al.  Cardiovascular manifestations of mixed connective tissue disease in adults. , 1983, Circulation.

[35]  J. Mclaughlin,et al.  Incidence of cancer among patients with systemic sclerosis , 1995, Cancer.

[36]  O. Nyrén,et al.  Risk of cancers of the oesophagus and stomach by histology or subsite in patients hospitalised for pernicious anaemia , 2003, Gut.

[37]  P. Lazzerini,et al.  Connective tissue diseases and cardiac rhythm disorders: an overview. , 2006, Autoimmunity reviews.

[38]  Brämer Gr International statistical classification of diseases and related health problems. Tenth revision. , 1988, World health statistics quarterly. Rapport trimestriel de statistiques sanitaires mondiales.

[39]  I. Fentiman,et al.  Systemic Lupus Erythematosus and Breast Cancer , 2008, The breast journal.

[40]  E. C. Harris,et al.  Suicide as an outcome for mental disorders , 1997, British Journal of Psychiatry.

[41]  E. Mittendorfer-Rutz,et al.  Diagnosis-specific disability pension and risk of all-cause and cause-specific mortality – a cohort study of 4.9 million inhabitants in Sweden , 2014, BMC Public Health.

[42]  A. Barabasi,et al.  Uncovering disease-disease relationships through the incomplete interactome , 2015, Science.

[43]  X. Mariette,et al.  Autoimmune and inflammatory disorders and risk of malignant lymphomas – an update , 2008, Journal of internal medicine.