title: Ultra-high dimensional variable selection with application to normative aging study: DNA methylation and metabolic syndrome.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Statistics, Northwestern University, 2006 Sheridan Road, Evanston, 60201, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Center for Applied Mathematics, Tianjin University, 92 Weijin Road, Tianjin, 300072, China.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Joyce
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, University of Minnesota, 420 Delaware, Minneapolis, 55455, USA.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: Department of Environmental Health, Harvard University, 677 Huntington Avenue, Boston, 02115, USA.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Department of Statistics, Northwestern University, 2006 Sheridan Road, Evanston, 60201, USA.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Environmental Health, Harvard University, 677 Huntington Avenue, Boston, 02115, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Preventive Medicine and Epidemiology, Boston University, 801 Massachusetts Avenue, Boston, 02118, USA.
authors.forename: Pantel S
authors.initials: PS
authors.lastname: Vokonas
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Preventive Medicine, Northwestern University, 680 N Lake Shore Drive, Chicago, 60611, USA. lei.liu@northwestern.edu.
authors.forename: Lei
authors.identifier: http://orcid.org/0000-0003-1844-338X
authors.initials: L
authors.lastname: Liu
mesh_terms: D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics*; D015233:Models, Statistical
keywords: Bootstrap; ISIS; Metabolic syndrome; Ultra-high dimensional variable selection; elastic net; methylation