Dataset Information

Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records.

ABSTRACT: Autoimmune diseases represent a significant medical burden affecting up to 5-8% of the U.S. POPULATION:While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, and a single disease approach. Here we performed a targeted genetic association study for cases of multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease (CD) to assess which common genetic variants contribute individually and pleiotropically to disease risk. Joint modeling and pathway analysis combining the three phenotypes were performed to identify common underlying mechanisms of risk of autoimmune conditions. European American cases of MS, RA, and CD, (n = 119, 53, and 129, respectively) and 1924 controls were identified using de-identified electronic health records (EHRs) through a combination of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) billing codes, Current Procedural Terminology (CPT) codes, medication lists, and text matching. As expected, hallmark SNPs in MS, such as DQA1 rs9271366 (OR = 1.91; p = 0.008), replicated in the present study. Both MS and CD were associated with TIMMDC1 rs2293370 (OR = 0.27, p = 0.01; OR = 0.25, p = 0.02; respectively). Additionally, PDE2A rs3781913 was significantly associated with both CD and RA (OR = 0.46, p = 0.02; OR = 0.32, p = 0.02; respectively). Joint modeling and pathway analysis identified variants within the KEGG NOD-like receptor signaling pathway and Shigellosis pathway as being correlated with the combined autoimmune phenotype. Our study replicated previously-reported genetic associations for MS and CD in a population derived from de-identified EHRs. We found evidence to support a shared genetic etiology between CD/MS and CD/RA outside of the major histocompatibility complex region and identified KEGG pathways indicative of a bacterial pathogenesis risk for autoimmunity in a joint model. Future work to elucidate this shared etiology will be key in the development of risk models as envisioned in the era of precision medicine.

SUBMITTER: Restrepo NA

PROVIDER: S-EPMC5071319 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records.

Restrepo Nicole A NA Butkiewicz Mariusz M McGrath Josephine A JA Crawford Dana C DC

Frontiers in genetics 20161020

Autoimmune diseases represent a significant medical burden affecting up to 5-8% of the U.S.<h4>Population</h4>While genetics is known to play a role, studies of common autoimmune diseases are complicated by phenotype heterogeneity, limited sample sizes, and a single disease approach. Here we performed a targeted genetic association study for cases of multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease (CD) to assess which common genetic variants contribute individually and pl ...[more]

PMID: 27812365

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Project description:BackgroundPatterns 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 an identification of temporal trends.MethodsMotivated 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 conclusionsAlthough 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.

Project description:BackgroundMental health supported housing services are a key component in the rehabilitation of people with severe and complex needs. They are implemented widely in the UK and other deinstitutionalised countries but there have been few empirical studies of their effectiveness due to the logistic challenges and costs of standard research methods. The Clinical Record Interactive Search (CRIS) tool, developed to de-identify and interrogate routinely recorded electronic health records, may provide an alternative to evaluate supported housing services.MethodsThe feasibility of using the Camden and Islington NHS Foundation Trust CRIS database to identify a sample of users of mental health supported accommodation services. Two approaches to data interrogation and case identification were compared; using structured fields indicating individual's accommodation status, and iterative development of free text searches of clinical notes referencing supported housing. The data used were recorded over a 10-year-period (01-January-2008 to 31-December-2017).ResultsBoth approaches were carried out by one full-time researcher over four weeks (150 hours). Two structured fields indicating accommodation status were found, 2,140 individuals had a value in at least one of the fields representative of supported accommodation. The free text search of clinical notes returned 21,103 records pertaining to 1,105 individuals. A manual review of 10% of the notes indicated an estimated 733 of these individuals had used a supported housing service, a positive predictive value of 66.4%. Over two-thirds of the individuals returned in the free text search (768/1,105, 69.5%) were identified via the structured fields approach. Although the estimated positive predictive value was relatively high, a substantial proportion of the individuals appearing only in the free text search (337/1,105, 30.5%) are likely to be false positives.ConclusionsIt is feasible and requires minimal resources to use de-identified electronic health record search tools to identify large samples of users of mental health supported housing using structured and free text fields. Further work is needed to establish the availability and completion of variables relevant to specific clinical research questions in order to fully assess the utility of electronic health records in evaluating the effectiveness of these services.

Project description:Previous candidate gene and genome-wide association studies have identified common genetic variants in LPA associated with the quantitative trait Lp(a), an emerging risk factor for cardiovascular disease. These associations are population-specific and many have not yet been tested for association with the clinical outcome of interest. To fill this gap in knowledge, we accessed the epidemiologic Third National Health and Nutrition Examination Surveys (NHANES III) and BioVU, the Vanderbilt University Medical Center biorepository linked to de-identified electronic health records (EHRs), including billing codes (ICD-9-CM) and clinical notes, to test population-specific Lp(a)-associated variants for an association with myocardial infarction (MI) among African Americans. We performed electronic phenotyping among African Americans in BioVU?40 years of age using billing codes. At total of 93 cases and 522 controls were identified in NHANES III and 265 cases and 363 controls were identified in BioVU. We tested five known Lp(a)-associated genetic variants (rs1367211, rs41271028, rs6907156, rs10945682, and rs1652507) in both NHANES III and BioVU for association with myocardial infarction. We also tested LPA rs3798220 (I4399M), previously associated with increased levels of Lp(a), MI, and coronary artery disease in European Americans, in BioVU. After meta-analysis, tests of association using logistic regression assuming an additive genetic model revealed no significant associations (p<0.05) for any of the five LPA variants previously associated with Lp(a) levels in African Americans. Also, I4399M rs3798220 was not associated with MI in African Americans (odds ratio = 0.51; 95% confidence interval: 0.16 - 1.65; p=0.26) despite strong, replicated associations with MI and coronary artery disease in European American genome-wide association studies. These data highlight the challenges in translating quantitative trait associations to clinical outcomes in diverse populations using large epidemiologic and clinic-based collections as envisioned for the Precision Medicine Initiative.

Dataset Information

Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records.

Publications

Shared Genetic Etiology of Autoimmune Diseases in Patients from a Biorepository Linked to De-identified Electronic Health Records.

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