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No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles

Abstract

In this paper it was investigated if any genotypic footprints from the fat mass and obesity associated (FTO) SNP could be found in 600 MHz 1H CPMG NMR profiles of around 1,000 human plasma samples from healthy Danish twins. The problem was addressed with a combination of univariate and multivariate methods. The NMR data was substantially compressed using principal component analysis or multivariate curve resolution-alternating least squares with focus on chemically meaningful feature selection reflecting the nature of chemical signals in an NMR spectrum. The possible existence of an FTO signature in the plasma samples was investigated at the subject level using supervised multivariate classification in the form of extended canonical variate analysis, classification tree modeling and Lasso (L1) regularized linear logistic regression model (GLMNET). Univariate hypothesis testing of peak intensities was used to explore the genotypic effect on the plasma at the population level. The multivariate classification approaches indicated poor discriminative power of the metabolic profiles whereas univariate hypothesis testing provided seven spectral regions with p < 0.05. Applying false discovery rate control, no reliable markers could be identified, which was confirmed by test set validation. We conclude that it is very unlikely that an FTO-correlated signal can be identified in these 1H CPMG NMR plasma metabolic profiles and speculate that high-throughput un-targeted genotype-metabolic correlations will in many cases be a difficult path to follow.

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Acknowledgments

The GEMINAKAR study was supported by grants from the Danish Medical Research Fund, the Danish Diabetes Association, the NOVO Foundation, the Danish Heart Foundation, and Apotekerfonden. The present study was supported by the Diogenes study which is the acronym for “Diet, Obesity and Genes” supported by the European Community (Contract no. FP6-513946), http://www.diogenes-eu.org/. The study was part of the research in The Danish Obesity Research Centre, DanORC (http://www.danorc.dk).

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Correspondence to M. A. Rasmussen.

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Kjeldahl, K., Rasmussen, M.A., Hasselbalch, A.L. et al. No genetic footprints of the fat mass and obesity associated (FTO) gene in human plasma 1H CPMG NMR metabolic profiles. Metabolomics 10, 132–140 (2014). https://doi.org/10.1007/s11306-013-0560-7

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  • DOI: https://doi.org/10.1007/s11306-013-0560-7

Keywords

  • FTO
  • NMR
  • CPMG
  • Data compression
  • ECVA
  • MCR-ALS