Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records

• Published in: Journal of intellectual disability research 2024-05, Vol.68 (5), p.491-511
• Main Authors: Nguyen, T. Q., Kerley, C. I., Key, A. P., Maxwell‐Horn, A. C., Wells, Q. S., Neul, J. L., Cutting, L. E., Landman, B. A.
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; behavioural phenotypes; Cardiovascular disease; Cardiovascular diseases; Cognition; Computerized medical records; Congenital diseases; Congenital heart disease; Down Syndrome; Electronic Health Records; Female; Health; Health Conditions; Heart Defects, Congenital - complications; Heart Disorders; Heart failure; Heart Failure - complications; Humans; Hypertension; Hypothyroidism; intellectual difference; Intervention; Language Impairments; Male; Medical records; Metabolism; methodology in research; Organic Chemistry; Phenotypes; Prediction models; Pulmonary hypertension; Records (Forms); Speech; Surgery
• ISSN: 0964-2633; 1365-2788
• DOI: 10.1111/jir.13124

Background Individuals with Down syndrome (DS) have a heightened risk for various co‐occurring health conditions, including congenital heart disease (CHD). In this two‐part study, electronic medical records (EMRs) were leveraged to examine co‐occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). Methods De‐identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one‐by‐two sex and age matched with samples of case–controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome‐disease association study (PheDAS) strategy was employed to reveal co‐occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case–controls. Data were included in predictive models and assessed which model‐based health conditions, when more prevalent, would increase the likelihood of surgical intervention. Results In Study 1, relative to case–controls and those with other IDDs, co‐occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co‐occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non‐rheumatic aortic valve disorders and heart failure (circulatory); acid–base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased