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PLoS Comput Biol. 2016 Apr 26;12(4):e1004885. doi: 10.1371/journal.pcbi.1004885. eCollection 2016 Apr.

Constraints on Biological Mechanism from Disease Comorbidity Using Electronic Medical Records and Database of Genetic Variants.

Author information

1
Department of Genetics, Stanford University, Stanford, California, United States of America.
2
UCSF Institute for Computational Health Sciences, San Francisco, California, United States of America.
3
Personalis, Inc., Menlo Park, California, United States of America.
4
Department of Bioengineering, Stanford University, Stanford, California, United States of America.

Abstract

Patterns of disease co-occurrence that deviate from statistical independence may represent important constraints on biological mechanism, which sometimes can be explained by shared genetics. In this work we study the relationship between disease co-occurrence and commonly shared genetic architecture of disease. Records of pairs of diseases were combined from two different electronic medical systems (Columbia, Stanford), and compared to a large database of published disease-associated genetic variants (VARIMED); data on 35 disorders were available across all three sources, which include medical records for over 1.2 million patients and variants from over 17,000 publications. Based on the sources in which they appeared, disease pairs were categorized as having predominant clinical, genetic, or both kinds of manifestations. Confounding effects of age on disease incidence were controlled for by only comparing diseases when they fall in the same cluster of similarly shaped incidence patterns. We find that disease pairs that are overrepresented in both electronic medical record systems and in VARIMED come from two main disease classes, autoimmune and neuropsychiatric. We furthermore identify specific genes that are shared within these disease groups.

PMID:
27115429
PMCID:
PMC4846031
DOI:
10.1371/journal.pcbi.1004885
[Indexed for MEDLINE]
Free PMC Article

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