Research Article: Age-dependent co-dependency structure of biomarkers in the general population of the United States

Date Published: March 15, 2019

Publisher: Impact Journals

Author(s): Alan Le Goallec, Chirag J. Patel.


Phenotypic biomarkers (e.g. cholesterol, weight, and glucose) are important to diagnose and treat diseases associated with aging. However, while many biomarkers are co-dependent (e.g. glycohemoglobin and glucose), it is generally unknown how age influences their co-dependence. In the following, we analyzed 50 biomarkers in 27,508 National Health and Nutrition Examination Survey (NHANES) participants (age range: 20 to 80, mean age: 46.3 years old, sexes: 48.9% males, 51.1% females, ethnicities: 46.0% Whites, 27.8% Hispanics, 20.0% non-Hispanic Blacks, 6.1% others) to investigate how the co-dependency structure of common biomarkers evolves with age and whether differences exist between sexes and ethnicities. First, we associated the change in correlations between biomarkers with chronological age. We identified six trends and replicated our top finding (height vs. systolic blood pressure) in participants of the UK Biobank (N=470,895). We found that, on average, correlations tend to decrease with age. Secondly, we examined how biomarkers predict other biomarkers in participants of different age groups. We found 17 (34%) biomarkers whose predictability decreases with age and 5 (10%) biomarkers whose predictability increases with age. A limitation of this study is that it cannot distinguish between biological changes related to aging and generational effects. Our results can be interactively explored here:

Partial Text

Human biomarkers such as blood biomarkers (e.g. glucose, LDL-cholesterol, HDL-cholesterol, albumin) and anthropomorphic measures (e.g. blood pressure, BMI (body mass index), arm circumference) are of paramount importance for medicine and biomedical research, as they are used to diagnose disease, evaluate treatment, predict a clinical outcome, and even serve as proxy for clinical endpoints [1]. These biomarkers change markedly with age [2–6]. Further still, it is hypothesized that these biomarkers can predict age [6–9]. However, it is less understood how, in fact, the inter-dependencies of biomarkers themselves change with age.

In summary, we have shown that the co-dependency structure of biomarkers changes as humans age. Further, we have evidence to support that the structure is different in males and females and between ethnicities. In general, differences between sexes are stronger than differences between ethnicities, and more differences were found between non-Hispanic Whites and non-Hispanic Blacks than between non-Hispanic Whites and Hispanics.




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