title: Genetic associations with micronutrient levels identified in immune and gastrointestinal networks.
abstract: The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6-14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein-protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene-nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions.
authors.affiliation: The Microsoft Research - University of Trento Centre for Computational and Systems Biology (COSBI), Rovereto, Italy.
authors.forename: Melissa J
authors.initials: MJ
authors.lastname: Morine
authors.forename: Jacqueline Pontes
authors.initials: JP
authors.lastname: Monteiro
authors.forename: Carolyn
authors.initials: C
authors.lastname: Wise
authors.forename: Candee
authors.initials: C
authors.lastname: Teitel
authors.forename: Lisa
authors.initials: L
authors.lastname: Pence
authors.forename: Anna
authors.initials: A
authors.lastname: Williams
authors.forename: Baitang
authors.initials: B
authors.lastname: Ning
authors.forename: Beverly
authors.initials: B
authors.lastname: McCabe-Sellers
authors.forename: Catherine
authors.initials: C
authors.lastname: Champagne
authors.forename: Jerome
authors.initials: J
authors.lastname: Turner
authors.forename: Beatrice
authors.initials: B
authors.lastname: Shelby
authors.forename: Margaret
authors.initials: M
authors.lastname: Bogle
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.forename: Corrado
authors.initials: C
authors.lastname: Priami
authors.forename: Jim
authors.initials: J
authors.lastname: Kaput