title: CardioGxE, a catalog of gene-environment interactions for cardiometabolic traits.
abstract: BACKGROUND
  Genetic understanding of complex traits has developed immensely over the past decade but remains hampered by incomplete descriptions of contribution to phenotypic variance. Gene-environment (GxE) interactions are one of these contributors and in the guise of diet and physical activity are important modulators of cardiometabolic phenotypes and ensuing diseases.
  
  
  RESULTS
  We mined the scientific literature to collect GxE interactions from 386 publications for blood lipids, glycemic traits, obesity anthropometrics, vascular measures, inflammation and metabolic syndrome, and introduce CardioGxE, a gene-environment interaction resource. We then analyzed the genes and SNPs supporting cardiometabolic GxEs in order to demonstrate utility of GxE SNPs and to discern characteristics of these important genetic variants. We were able to draw many observations from our extensive analysis of GxEs. 1) The CardioGxE SNPs showed little overlap with variants identified by main effect GWAS, indicating the importance of environmental interactions with genetic factors on cardiometabolic traits. 2) These GxE SNPs were enriched in adaptation to climatic and geographical features, with implications on energy homeostasis and response to physical activity. 3) Comparison to gene networks responding to plasma cholesterol-lowering or regression of atherosclerotic plaques showed that GxE genes have a greater role in those responses, particularly through high-energy diets and fat intake, than do GWAS-identified genes for the same traits. Other aspects of the CardioGxE dataset were explored.
  
  
  CONCLUSIONS
  Overall, we demonstrate that SNPs supporting cardiometabolic GxE interactions often exhibit transcriptional effects or are under positive selection. Still, not all such SNPs can be assigned potential functional or regulatory roles often because data are lacking in specific cell types or from treatments that approximate the environmental factor of the GxE. With research on metabolic related complex disease risk embarking on genome-wide GxE interaction tests, CardioGxE will be a useful resource.
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Britt A
authors.initials: BA
authors.lastname: Blokker
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Hassan S
authors.initials: HS
authors.lastname: Dashti
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Paula-Dene
authors.initials: PD
authors.lastname: Nesbeth
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Brittany Elle
authors.initials: BE
authors.lastname: Cooper
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Yiyi
authors.initials: Y
authors.lastname: Ma
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Ruixue
authors.initials: R
authors.lastname: Hou
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: Kris
authors.initials: K
authors.lastname: Richardson
authors.affiliation: JM-USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
keywords: Cardiovascular diseases; Diet; Gene-environment interaction; Genetic variants; Phenotypic variance; Physical activity; Type 2 diabetes