Data-driven discovery of seasonally linked diseases from an Electronic Health Records system

BACKGROUND: Patterns of disease incidence can identify new risk factors for the disease or provide insight into the etiology. For example, allergies and infectious diseases have been shown to follow periodic temporal patterns due to seasonal changes in environmental or infectious agents. Previous work searching for seasonal or other temporal patterns in disease diagnosis rates has been limited both in the scope of the diseases examined and in the ability to distinguish unexpected seasonal patterns. Electronic Health Records (EHR) compile extensive longitudinal clinical information, constituting a unique source for discovery of trends in occurrence of disease. However, the data suffer from inherent biases that preclude a identification of temporal trends. METHODS: Motivated by observation of the biases in this data source, we developed a method (Lomb-Scargle periodograms in detrended data, LSP-detrend) to find periodic patterns by adjusting the temporal information for broad trends in incidence, as well as seasonal changes in total hospitalizations. LSP-detrend can sensitively uncover periodic temporal patterns in the corrected data and identify the significance of the trend. We apply LSP-detrend to a compilation of records from 1.5 million patients encoded by ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification), including 2,805 disorders with more than 500 occurrences across a 12 year period, recorded from 1.5 million patients. RESULTS AND CONCLUSIONS: Although EHR data, and ICD-9 coded records in particular, were not created with the intention of aggregated use for research, these data can in fact be mined for periodic patterns in incidence of disease, if confounders are properly removed. Of all diagnoses, around 10% are identified as seasonal by LSP-detrend, including many known phenomena. We robustly reproduce previous findings, even for relatively rare diseases. For instance, Kawasaki disease, a rare childhood disease that has been associated with weather patterns, is detected as strongly linked with winter months. Among the novel results, we find a bi-annual increase in exacerbations of myasthenia gravis, a potentially life threatening complication of an autoimmune disease. We dissect the causes of this seasonal incidence and propose that factors predisposing patients to this event vary through the year.