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Gene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.

TitleGene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.
Publication TypeJournal Article
Year of Publication2015
AuthorsDashti, HS, Follis, JL, Smith, CE, Tanaka, T, Garaulet, M, Gottlieb, DJ, Hruby, A, Jacques, PF, de Jong, JCKiefte-, Lamon-Fava, S, Scheer, FAJL, Bartz, TM, Kovanen, L, Wojczynski, MK, Frazier-Wood, AC, Ahluwalia, TS, Perälä, M-M, Jonsson, A, Muka, T, Kalafati, IP, Mikkilä, V, Ordovas, JM
Corporate/Institutional AuthorsCHARGE Nutrition Study Group
JournalDiabetes Care
Date Published2015 Aug
KeywordsAdult, Alleles, Blood Glucose, Circadian Rhythm Signaling Peptides and Proteins, Cohort Studies, Diabetes Mellitus, Type 2, Diet, Fat-Restricted, European Continental Ancestry Group, Fasting, Female, Gene-Environment Interaction, Humans, Insulin Resistance, Male, Middle Aged, Multicenter Studies as Topic, Observational Studies as Topic, Phenotype, Polymorphism, Single Nucleotide, Sleep, Waist Circumference
Abstract<p><b>OBJECTIVE: </b>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.</p><p><b>RESEARCH DESIGN AND METHODS: </b>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.</p><p><b>RESULTS: </b>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).</p><p><b>CONCLUSIONS: </b>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.</p>
Alternate JournalDiabetes Care
PubMed ID26084345
PubMed Central IDPMC4512139
Grant ListDK063491 / DK / NIDDK NIH HHS / United States
HHSN268200800007C / / PHS HHS / United States
K08-HL-112845-01 / HL / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 HL117078 / HL / NHLBI NIH HHS / United States
R01-HL-094806 / HL / NHLBI NIH HHS / United States
R21-DK-089378 / DK / NIDDK NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States