Age, Sex, Body Mass Index, Diet and Menopause Related Metabolites in a Large Homogeneous Alpine Cohort.

Vinicius Verri Hernandes,Martin Gögele,Sigurður Vidir Smárason,Essi Marjatta Hantikainen,Ilaria Bozzolan,Giulia Caprioli,Peter P Pramstaller,Johannes Rainer,Baldur Bragi Sigurdsson,Vanessa Garcia-Larsen,Nikola Dordevic

doi:10.3390/metabo12030205

Abstract

Metabolomics in human serum samples provide a snapshot of the current metabolic state of an individuum. Metabolite concentrations are influenced by both genetic and environmental factors. Concentrations of certain metabolites can further depend on age, sex, menopause, and diet of study participants. A better understanding of these relationships is pivotal for the planning of metabolomics studies involving human subjects and interpretation of their results. We generated one of the largest single-site targeted metabolomics data sets consisting of 175 quantified metabolites in 6872 study participants. We identified metabolites significantly associated with age, sex, body mass index, diet, and menopausal status. While most of our results agree with previous large-scale studies, we also found novel associations including serotonin as a sex and BMI-related metabolite and sarcosine and C2 carnitine showing significantly higher concentrations in post-menopausal women. Finally, we observed strong associations between higher consumption of food items and certain metabolites, mostly phosphatidylcholines and lysophosphatidylcholines. Most, and the strongest, relationships were found for habitual meat intake while no significant relationships were found for most fruits, vegetables, and grain products. Summarizing, our results reconfirm findings from previous population-based studies on an independent cohort. Together, these findings will ultimately enable the consolidation of sets of metabolites which are related to age, sex, BMI, and menopause as well as to participants’ diet.

Highlights

Metabolomics is as a powerful tool for phenotypic characterization of individuals, providing an unprecedented understanding of the molecular basis of human health
We created a targeted metabolomics data-set for 6872 participants of the Cooperative Health Research in South Tyrol (CHRIS) study [22] consisting of the quantification of 175 metabolites measured on 88 plates (see Table S3 for a listing of all metabolites including their names, aliases, chemical formulas and Human Metabolome Database (HMDB, https://hmdb.ca/, accessed on 1 February 2022) identifiers and Table 1 for the demographic characteristics of the study participants)
Metabolites 2022, 12, 205 on values measured in different quality control (QC) samples in the same batch, which reduced between-batch differences considerably, especially for the data acquired with flow injection analysis

Summary

Introduction

Metabolomics is as a powerful tool for phenotypic characterization of individuals, providing an unprecedented understanding of the molecular basis of human health. Among the many challenges related to the design of an epidemiological-metabolomics study, one of vital importance is the assessment of the various sources of data variability that may interfere with the results and cause spurious or incorrect conclusions [1]. This is even more important for smaller-sized studies typically conducted in the clinical setting and, due to their size, are potentially more affected by an imbalanced or inappropriate study design. Some of the largest studies investigated the relationship between metabolites and menopause status, including ALSPAC [18] (sex and menopause-related metabolites, 14,541 individuals), and the Northern European cohorts [19] (age-, sex-, menopause-related metabolites, 26,065 individuals)

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Results

Conclusion