Victoria Higgins1, Shabnam Hooshmand2, Khosrow Adeli3. 1. CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. 2. CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada. 3. CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Laboratory Medicine & Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: khosrow.adeli@sickkids.ca.
Abstract
BACKGROUND: Reference intervals (i.e. normative ranges) established from a healthy reference population are essential to accurately interpret disease biomarkers. Biomarker concentration may partially depend on associations with other biomarkers due to various physiological and pathophysiological processes. In this study, a robust correlation analysis was performed to identify physiological biomarker associations in the healthy pediatric CALIPER cohort. METHODS: Population reference values for 35 biochemical and 20 fertility/endocrine markers were analyzed for correlations in all subjects, male adolescents, female adolescents, and young children. Associations between biomarkers were assessed by Spearman's rank correlation and a multivariate analysis technique, principal component analysis (PCA). RESULTS: Of 197, 90, 59, and 32 significant correlations between biochemical markers in all subjects, male adolescents, female adolescents, and children, respectively, 23, 19, 16, and 9 were moderately strong (r > 0.5 or r < -0.5). Of 98, 24, 33, and 16 significant correlations between fertility/endocrine markers in all subjects, male adolescents, female adolescents, and children, respectively, 17, 8, 11, and 5 were moderately strong. Results were agreeable between Spearman's rank method and PCA. In some cases, biomarker correlations differed between sexes. CONCLUSIONS: Using PCA, this study provides for the first time an extensive analysis of circulating biomarker associations in a healthy pediatric cohort. These data can inform future studies of potential confounding factors or particular variables that should be considered in test result interpretation for specific diseases.
BACKGROUND: Reference intervals (i.e. normative ranges) established from a healthy reference population are essential to accurately interpret disease biomarkers. Biomarker concentration may partially depend on associations with other biomarkers due to various physiological and pathophysiological processes. In this study, a robust correlation analysis was performed to identify physiological biomarker associations in the healthy pediatric CALIPER cohort. METHODS: Population reference values for 35 biochemical and 20 fertility/endocrine markers were analyzed for correlations in all subjects, male adolescents, female adolescents, and young children. Associations between biomarkers were assessed by Spearman's rank correlation and a multivariate analysis technique, principal component analysis (PCA). RESULTS: Of 197, 90, 59, and 32 significant correlations between biochemical markers in all subjects, male adolescents, female adolescents, and children, respectively, 23, 19, 16, and 9 were moderately strong (r > 0.5 or r < -0.5). Of 98, 24, 33, and 16 significant correlations between fertility/endocrine markers in all subjects, male adolescents, female adolescents, and children, respectively, 17, 8, 11, and 5 were moderately strong. Results were agreeable between Spearman's rank method and PCA. In some cases, biomarker correlations differed between sexes. CONCLUSIONS: Using PCA, this study provides for the first time an extensive analysis of circulating biomarker associations in a healthy pediatric cohort. These data can inform future studies of potential confounding factors or particular variables that should be considered in test result interpretation for specific diseases.