Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Methylation-Wide Human Study Identified Age and BMI-Independent Association of Differentially Methylated Regions and Leukocyte Telomere Length

Version 1 : Received: 23 June 2021 / Approved: 24 June 2021 / Online: 24 June 2021 (15:47:38 CEST)

How to cite: Nicoletti, C.F.; Noronha, N.Y.; Pinhel, M.A.S.; Nonino, C.B. Methylation-Wide Human Study Identified Age and BMI-Independent Association of Differentially Methylated Regions and Leukocyte Telomere Length. Preprints 2021, 2021060600 (doi: 10.20944/preprints202106.0600.v1). Nicoletti, C.F.; Noronha, N.Y.; Pinhel, M.A.S.; Nonino, C.B. Methylation-Wide Human Study Identified Age and BMI-Independent Association of Differentially Methylated Regions and Leukocyte Telomere Length. Preprints 2021, 2021060600 (doi: 10.20944/preprints202106.0600.v1).

Abstract

Background: Telomere length (TL) shortening process is associated with several known environment and individual determinants. DNA methylation is the most studied epigenetic process and may be associated with TL. We investigated the associations between DNA methylation and TL in peripheral blood. Methods: Methylation wide association study was conducted in 47 women (37.1±8.8 years) with different nutritional status. Association between TL and DNA methylation levels were explored by univariate and multiple linear regression models, corrected by age and Body Mass Index. Corrections for multiple comparisons by Benjamini‐Hochberg test was also performed. WEBGestalt was used to identify pathways that are responsible for regulating TL. Results: We found negative correlations between TL and BMI (r = -0.641; p = 0.001), abdominal circumference (r = -0.622; p = 0.001) and fat mass (r = -0.656; p = 0.001). 44 CpGs sites were associated with TL, independent of age and BMI. The most of these sites were negatively correlated with TL. For the 7 remained sites, DNA hypomethylation were associated with shorter TL. These CpGs were related to nine different pathways, including thermogenesis, cancer, glutamatergic and serotonergic synapse. Conclusion: There is an epigenetic contribution in TL, independent of nutritional status and age. Genes related to TL are involved in important metabolic pathways.

Subject Areas

telomere length; DNA methylation; DNA microarray

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