04354nas a2200661 4500008004100000022001400041245008900055210006900144260001300213300001200226490000700238520241500245653001002660653001202670653001802682653005302700653001902753653003002772653002502802653004002827653001202867653001102879653003302890653001102923653002302934653000902957653001602966653003302982653003503015653001403050653003603064653001003100653002403110100002203134700002003156700002003176700002003196700002003216700002403236700001703260700002103277700003203298700002503330700002503355700002003380700001903400700002403419700002803443700002803471700002403499700001803523700001803541700002403559700001903583700002103602710003303623856003603656 2015 eng d a1935-554800aGene-Environment Interactions of Circadian-Related Genes for Cardiometabolic Traits.0 aGeneEnvironment Interactions of CircadianRelated Genes for Cardi c2015 Aug a1456-660 v383 a
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.
RESEARCH DESIGN AND 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.
10aAdult10aAlleles10aBlood Glucose10aCircadian Rhythm Signaling Peptides and Proteins10aCohort Studies10aDiabetes Mellitus, Type 210aDiet, Fat-Restricted10aEuropean Continental Ancestry Group10aFasting10aFemale10aGene-Environment Interaction10aHumans10aInsulin Resistance10aMale10aMiddle Aged10aMulticenter Studies as Topic10aObservational Studies as Topic10aPhenotype10aPolymorphism, Single Nucleotide10aSleep10aWaist Circumference1 aDashti, Hassan, S1 aFollis, Jack, L1 aSmith, Caren, E1 aTanaka, Toshiko1 aGaraulet, Marta1 aGottlieb, Daniel, J1 aHruby, Adela1 aJacques, Paul, F1 ade Jong, Jessica, C Kiefte-1 aLamon-Fava, Stefania1 aScheer, Frank, A J L1 aBartz, Traci, M1 aKovanen, Leena1 aWojczynski, Mary, K1 aFrazier-Wood, Alexis, C1 aAhluwalia, Tarunveer, S1 aPerälä, Mia-Maria1 aJonsson, Anna1 aMuka, Taulant1 aKalafati, Ioanna, P1 aMikkilä, Vera1 aOrdovas, Jose, M1 aCHARGE Nutrition Study Group uhttps://chs-nhlbi.org/node/692703656nas a2200433 4500008004100000022001400041245009700055210006900152260001600221520237300237100002202610700001802632700002402650700001702674700002002691700002002711700002302731700002102754700002002775700002002795700002002815700001702835700002302852700002402875700002402899700002302923700001902946700001102965700002402976700002003000700002903020700002703049700002503076700002503101700002203126700002003148700001803168856003603186 2019 eng d a1938-320700aGenome-wide association study of breakfast skipping links clock regulation with food timing.0 aGenomewide association study of breakfast skipping links clock r c2019 Jun 133 aBACKGROUND: Little is known about the contribution of genetic variation to food timing, and breakfast has been determined to exhibit the most heritable meal timing. As breakfast timing and skipping are not routinely measured in large cohort studies, alternative approaches include analyses of correlated traits.
OBJECTIVES: The aim of this study was to elucidate breakfast skipping genetic variants through a proxy-phenotype genome-wide association study (GWAS) for breakfast cereal skipping, a commonly assessed correlated trait.
METHODS: We leveraged the statistical power of the UK Biobank (n = 193,860) to identify genetic variants related to breakfast cereal skipping as a proxy-phenotype for breakfast skipping and applied several in silico approaches to investigate mechanistic functions and links to traits/diseases. Next, we attempted validation of our approach in smaller breakfast skipping GWAS from the TwinUK (n = 2,006) and the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium (n = 11,963).
RESULTS: In the UK Biobank, we identified 6 independent GWAS variants, including those implicated for caffeine (ARID3B/CYP1A1), carbohydrate metabolism (FGF21), schizophrenia (ZNF804A), and encoding enzymes important for N6-methyladenosine RNA transmethylation (METTL4, YWHAB, and YTHDF3), which regulates the pace of the circadian clock. Expression of identified genes was enriched in the cerebellum. Genome-wide correlation analyses indicated positive correlations with anthropometric traits. Through Mendelian randomization (MR), we observed causal links between genetically determined breakfast skipping and higher body mass index, more depressive symptoms, and smoking. In bidirectional MR, we demonstrated a causal link between being an evening person and skipping breakfast, but not vice versa. We observed association of our signals in an independent breakfast skipping GWAS in another British cohort (P = 0.032), TwinUK, but not in a meta-analysis of non-British cohorts from the CHARGE consortium (P = 0.095).
CONCLUSIONS: Our proxy-phenotype GWAS identified 6 genetic variants for breakfast skipping, linking clock regulation with food timing and suggesting a possible beneficial role of regular breakfast intake as part of a healthy lifestyle.
1 aDashti, Hassan, S1 aMerino, Jordi1 aLane, Jacqueline, M1 aSong, Yanwei1 aSmith, Caren, E1 aTanaka, Toshiko1 aMcKeown, Nicola, M1 aTucker, Chandler1 aSun, Dianjianyi1 aBartz, Traci, M1 aLi-Gao, Ruifang1 aNisa, Hoirun1 aReutrakul, Sirimon1 aLemaitre, Rozenn, N1 aAlshehri, Tahani, M1 ade Mutsert, Renée1 aBazzano, Lydia1 aQi, Lu1 aKnutson, Kristen, L1 aPsaty, Bruce, M1 aMook-Kanamori, Dennis, O1 aPerica, Vesna, Boraska1 aNeuhouser, Marian, L1 aScheer, Frank, A J L1 aRutter, Martin, K1 aGaraulet, Marta1 aSaxena, Richa uhttps://chs-nhlbi.org/node/8099