Leveraging Epidemiologic and Clinical Collections for Genomic Studies of Complex Traits

Abstract

Background/Aims: Present-day limited resources demand DNA and phenotyping alternatives to the traditional prospective population-based epidemiologic collections. Methods: To accelerate genomic discovery with an emphasis on diverse populations, we - as part of the Epidemiologic Architecture for Genes Linked to Environment (EAGLE) study - accessed all non-European American samples (n = 15,863) available in BioVU, the Vanderbilt University biorepository linked to de-identified electronic medical records, for genomic studies as part of the larger Population Architecture using Genomics and Epidemiology (PAGE) I study. Given previous studies have cautioned against the secondary use of clinically collected data compared with epidemiologically collected data, we present here a characterization of EAGLE BioVU, including the billing and diagnostic (ICD-9) code distributions for adult and pediatric patients as well as comparisons made for select health metrics (body mass index, glucose, HbA1c, HDL-C, LDL-C, and triglycerides) with the population-based National Health and Nutrition Examination Surveys (NHANES) linked to DNA samples (NHANES III, n = 7,159; NHANES 1999-2002, n = 7,839). Results: Overall, the distributions of billing and diagnostic codes suggest this clinical sample is a mixture of healthy and sick patients like that expected for a contemporary American population. Conclusion: Little bias is observed among health metrics, suggesting this clinical collection is suitable for genomic studies along with traditional epidemiologic cohorts.

Evidence for Extensive Pleiotropy Among Pharmacogenes

“…After quality control (see 'Methods'), the majority of the samples were European-American (n = 6067) and the remainder African-American (n = 762). Overall, 48% of the samples were female, slightly less than the 52% observed in BioVU overall [46]. The mean body mass index of this PheWAS study population was in the overweight category (28.34 kg/m 2 ), and the average age at last EHR record was 55 years (Table 1).…”

Trans-ethnic fine-mapping of genetic loci for body mass index in the diverse ancestral populations of the Population Architecture using Genomics and Epidemiology (PAGE) Study reveals evidence for multiple signals at established loci

“…In EAGLE BioVU, weight and height were calculated across the complete medical histories (Crawford et al 2015) following a published protocol (Goodloe et al in press). For BioMe, height and weight measures were obtained from participants’ medical records at the time of enrollment (Locke et al 2015; Monda et al 2013).…”

Development and Performance of Text-Mining Algorithms to Extract Socioeconomic Status From De-Identified Electronic Health Records

“…The study population included all racial/ethnic minority patients >18 years old participating in BioVU as of 2011 22 . The EHRs used for the development of the algorithms were updated in 2015 to include current information.…”