title: Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.
abstract: OBJECTIVE
  Common circadian-related gene variants associate with increased risk for metabolic alterations including type 2 diabetes. However, little is known about whether diet and sleep could modify associations between circadian-related variants (CLOCK-rs1801260, CRY2-rs11605924, MTNR1B-rs1387153, MTNR1B-rs10830963, NR1D1-rs2314339) and cardiometabolic traits (fasting glucose [FG], HOMA-insulin resistance, BMI, waist circumference, and HDL-cholesterol) to facilitate personalized recommendations.
  
  
  METHODS
  We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations and interactions between dietary intake/sleep duration and selected variants on cardiometabolic traits from 15 cohort studies including up to 28,190 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium.
  
  
  RESULTS
  We observed significant associations between relative macronutrient intakes and glycemic traits and short sleep duration (<7 h) and higher FG and replicated known MTNR1B associations with glycemic traits. No interactions were evident after accounting for multiple comparisons. However, we observed nominally significant interactions (all P < 0.01) between carbohydrate intake and MTNR1B-rs1387153 for FG with a 0.003 mmol/L higher FG with each additional 1% carbohydrate intake in the presence of the T allele, between sleep duration and CRY2-rs11605924 for HDL-cholesterol with a 0.010 mmol/L higher HDL-cholesterol with each additional hour of sleep in the presence of the A allele, and between long sleep duration (≥9 h) and MTNR1B-rs1387153 for BMI with a 0.60 kg/m(2) higher BMI with long sleep duration in the presence of the T allele relative to normal sleep duration (≥7 to <9 h).
  
  
  CONCLUSIONS
  Our results suggest that lower carbohydrate intake and normal sleep duration may ameliorate cardiometabolic abnormalities conferred by common circadian-related genetic variants. Until further mechanistic examination of the nominally significant interactions is conducted, recommendations applicable to the general population regarding diet—specifically higher carbohydrate and lower fat composition—and normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants.
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA hassan.dashti@tufts.edu.
authors.forename: Hassan S
authors.initials: HS
authors.lastname: Dashti
authors.affiliation: Department of Mathematics, Computer Science and Cooperative Engineering, University of St. Thomas, Houston, TX.
authors.forename: Jack L
authors.initials: JL
authors.lastname: Follis
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Physiology, University of Murcia, Murcia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Garaulet
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA Sleep Disorders Center, VA Boston Healthcare System, Boston, MA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Gottlieb
authors.affiliation: Department of Nutrition, Harvard School of Public Health, Boston, MA.
authors.forename: Adela
authors.initials: A
authors.lastname: Hruby
authors.affiliation: Nutritional Epidemiology Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Jacques
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands Global Public Health, Leiden University College, The Hague, the Netherlands.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Kiefte-de Jong
authors.affiliation: Cardiovascular Nutrition Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.affiliation: Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA Division of Sleep Medicine, Harvard Medical School, Boston, MA.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
authors.affiliation: Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA Department of Biostatistics, University of Washington, Seattle, WA.
authors.forename: Traci M
authors.initials: TM
authors.lastname: Bartz
authors.affiliation: Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Kovanen
authors.affiliation: Department of Genetics, Washington University School of Medicine, St. Louis, MO.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Wojczynski
authors.affiliation: U.S. Department of Agriculture/Agricultural Research Service Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.
authors.forename: Alexis C
authors.initials: AC
authors.lastname: Frazier-Wood
authors.affiliation: The Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Copenhagen Prospective Studies on Asthma in Childhood, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Danish Pediatric Asthma Centre, Gentofte Hospital, The Capital Region, Copenhagen, Denmark.
authors.forename: Tarunveer S
authors.initials: TS
authors.lastname: Ahluwalia
authors.affiliation: Department of Chronic Disease Prevention, National Institute for Health and Welfare (THL), Helsinki, Finland.
authors.forename: Mia-Maria
authors.initials: MM
authors.lastname: Perälä
authors.affiliation: The Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anna
authors.initials: A
authors.lastname: Jonsson
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors.forename: Taulant
authors.initials: T
authors.lastname: Muka
authors.affiliation: Department of Nutrition and Dietetics, Harokopio University, Athens, Greece.
authors.forename: Ioanna P
authors.initials: IP
authors.lastname: Kalafati
authors.affiliation: Department of Food and Environmental Sciences, Division of Nutrition, University of Helsinki, Helsinki, Finland Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
authors.forename: Vera
authors.initials: V
authors.lastname: Mikkilä
authors.affiliation: Nutrition and Genomics Laboratory, Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA Department of Epidemiology, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain Instituto Madrileño de Estudios Avanzados en Alimentación (IMDEA-FOOD), Madrid, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000328:Adult; D000483:Alleles; D001786:Blood Glucose / Q000378:metabolism; D056925:Circadian Rhythm Signaling Peptides and Proteins / Q000235:genetics*; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D018752:Diet, Fat-Restricted; D005215:Fasting / Q000097:blood; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D064887:Observational Studies as Topic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012890:Sleep / Q000502:physiology; D055105:Waist Circumference / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D001786:Blood Glucose; D056925:Circadian Rhythm Signaling Peptides and Proteins