TY - JOUR

T1 - Sexual dimorphism, age and fat mass are key phenotypic drivers of proteomic signatures

AU - Curran, Aoife M

AU - Fogarty Draper, Colleen

AU - Scott-Boyer, Marie-Pier

AU - Valsesia, Armand

AU - Roche, Helen M

AU - Ryan, Miriam F

AU - Gibney, Michael J

AU - Kutmon, Martina

AU - Evelo, Chris T

AU - Coort, Susan L

AU - Astrup, Arne

AU - Saris, Wim H

AU - Brennan, Lorraine

AU - Kaput, Jim

N1 - CURIS 2017 NEXS 271

PY - 2017

Y1 - 2017

N2 - Validated protein biomarkers are needed for assessing health trajectories, predicting and sub-classifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51 and 112 proteins (adjusted p<0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male v female) and continuous phenotypes (age, fat mass) which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.

AB - Validated protein biomarkers are needed for assessing health trajectories, predicting and sub-classifying disease, and optimizing diagnostic and therapeutic clinical decision-making. The sensitivity, specificity, accuracy, and precision of single or combinations of protein biomarkers may be altered by differences in physiological states limiting the ability to translate research results to clinically useful diagnostic tests. Aptamer based affinity assays were used to test whether low abundant serum proteins differed based on age, sex and fat mass in a healthy population of 94 males and 102 females from the MECHE cohort. The findings were replicated in 217 healthy male and 377 healthy female participants in the DiOGenes consortium. Of the 1129 proteins in the panel, 141, 51 and 112 proteins (adjusted p<0.1) were identified in the MECHE cohort and significantly replicated in DiOGenes for sexual dimorphism, age, and fat mass, respectively. Pathway analysis classified a subset of proteins from the 3 phenotypes to the complement and coagulation cascades pathways and to immune and coagulation processes. These results demonstrated that specific proteins were statistically associated with dichotomous (male v female) and continuous phenotypes (age, fat mass) which may influence the identification and use of biomarkers of clinical utility for health diagnosis and therapeutic strategies.

KW - Proteomics

KW - Phenotype

KW - Biomarker

KW - Sex

KW - Male

KW - Female

KW - Age

KW - Fat mass

KW - Protein

KW - Pathway

U2 - 10.1021/acs.jproteome.7b00501

DO - 10.1021/acs.jproteome.7b00501

M3 - Journal article

C2 - 28950061

VL - 16

SP - 4122

EP - 4133

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 11

ER -