, a bio/informatics shared resource is still "open for business" - Visit the CDS website


A study paradigm integrating prospective epidemiologic cohorts and electronic health records to identify disease biomarkers.

Mosley JD, Feng Q, Wells QS, Van Driest SL, Shaffer CM, Edwards TL, Bastarache L, Wei WQ, Davis LK, McCarty CA, Thompson W, Chute CG, Jarvik GP, Gordon AS, Palmer MR, Crosslin DR, Larson EB, Carrell DS, Kullo IJ, Pacheco JA, Peissig PL, Brilliant MH, Linneman JG, Namjou B, Williams MS, Ritchie MD, Borthwick KM, Verma SS, Karnes JH, Weiss ST, Wang TJ, Stein CM, Denny JC, Roden DM
Nat Commun. 2018 9 (1): 3522

PMID: 30166544 · PMCID: PMC6117367 · DOI:10.1038/s41467-018-05624-4

Defining the full spectrum of human disease associated with a biomarker is necessary to advance the biomarker into clinical practice. We hypothesize that associating biomarker measurements with electronic health record (EHR) populations based on shared genetic architectures would establish the clinical epidemiology of the biomarker. We use Bayesian sparse linear mixed modeling to calculate SNP weightings for 53 biomarkers from the Atherosclerosis Risk in Communities study. We use the SNP weightings to computed predicted biomarker values in an EHR population and test associations with 1139 diagnoses. Here we report 116 associations meeting a Bonferroni level of significance. A false discovery rateĀ (FDR)-based significance threshold reveals more known and undescribed associations across a broad range of biomarkers, including biometric measures, plasma proteins and metabolites, functional assays, and behaviors. We confirm an inverse association between LDL-cholesterol level and septicemia risk in an independent epidemiological cohort. This approach efficiently discovers biomarker-disease associations.

MeSH Terms (8)

Bayes Theorem Biomarkers Cholesterol, LDL Electronic Health Records Genome-Wide Association Study Humans Prospective Studies Risk Factors

Connections (1)

This publication is referenced by other Labnodes entities:

Links