Ultra-high dimensional variable selection with application to normative aging study: DNA methylation and metabolic syndrome

Grace Yoon, Yinan Zheng, Zhou Zhang, Haixiang Zhang, Tao Gao, Brian Joyce, Wei Zhang, Weihua Guan, Andrea A. Baccarelli, Wenxin Jiang, Joel Schwartz, Pantel S. Vokonas, Lifang Hou, Lei Liu

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Metabolic syndrome has become a major public health challenge worldwide. The association between metabolic syndrome and DNA methylation is of great research interest. Results: We constructed a binomial model to investigate the association between a metabolic syndrome index and DNA methylation in the Normative Aging Study. We applied the Iterative Sure Independence Screening (ISIS) method with elastic net penalty to DNA methylation levels at 484,548 CpG markers from 659 human subjects, and demonstrated that the screening step in ISIS can significantly improve the performance of the elastic net. Conclusion: The proposed method identifies four CpGs which can be mapped to two biologically relevant and functional genes. Identification of significant CpG markers may potentially have practical implications for disease prevention and treatment.

Original languageEnglish (US)
Article number156
JournalBMC bioinformatics
Issue number1
StatePublished - Mar 7 2017

Bibliographical note

Funding Information:
We are thankful to Dr. Jinchi Lv for helpful discussion and instruction on using the ISIS method. Funding This study was supported by AHA 14SFRN20480260, 12GRNT12070254 and National Institute of Environmental Health Sciences grant R01 ES015172. The VA Normative Aging Study is supported by the Cooperative Studies Program/Epidemiology Research and Information Center of the US Department of Veterans Affairs.

Publisher Copyright:
© 2017 The Author(s).

Copyright 2017 Elsevier B.V., All rights reserved.


  • Bootstrap
  • Elastic net
  • ISIS
  • Metabolic syndrome
  • Methylation
  • Ultra-high dimensional variable selection

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