TY - JOUR
T1 - Gene-environment interactions of circadian-related genes for cardiometabolic traits
AU - Dashti, Hassan S.
AU - Follis, Jack L.
AU - Smith, Caren E.
AU - Tanaka, Toshiko
AU - Garaulet, Marta
AU - Gottlieb, Daniel J.
AU - Hruby, Adela
AU - Jacques, Paul F.
AU - Kiefte-De Jong, Jessica C.
AU - Lamon-Fava, Stefania
AU - Scheer, Frank A.J.L.
AU - Bartz, Traci M.
AU - Kovanen, Leena
AU - Wojczynski, Mary K.
AU - Frazier-Wood, Alexis C.
AU - Ahluwalia, Tarunveer S.
AU - Perälä, Mia Maria
AU - Jonsson, Anna
AU - Muka, Taulant
AU - Kalafati, Ioanna P.
AU - Mikkilä, Vera
AU - Ordovás, José M.
N1 - Funding Information:
Funding. Infrastructure for the CHARGE Consortium is supported in part by the National Heart, Lung, and Blood Institute grant HHSN268200800007C. Support was provided by the U.S. Department of Agriculture, under agreement no. 58-1950-0-014, American Heart Association (grant 14BGIA18740011), Academy of Finland (grant 117787), Italian Ministry of Health (grant ICS110.1/RF97.71), National Institute of Diabetes and Digestive and Kidney Diseases (grant DK063491), National Center for Advancing Translational Sciences (grant UL1TR000124). C.E.S. is supported by K08-HL- 112845-01. F.A.J.L.S. was supported in part by National Institutes of Health grants R21-DK- 089378 and R01-HL-094806. Cohort-specific sources of support and acknowledgments are presented in Supplementary Table 1. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the U.S. Department of Agriculture.
Publisher Copyright:
©2015 by the American Diabetes Association.
PY - 2015/8
Y1 - 2015/8
N2 - 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-effectmeta-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 HDLcholesterol 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/m2 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 dietdspecifically higher carbohydrate and lower fat compositiondand normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants.
AB - 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-effectmeta-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 HDLcholesterol 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/m2 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 dietdspecifically higher carbohydrate and lower fat compositiondand normal sleep duration should continue to be emphasized among individuals with the investigated circadian-related gene variants.
UR - http://www.scopus.com/inward/record.url?scp=84962440593&partnerID=8YFLogxK
U2 - 10.2337/dc14-2709
DO - 10.2337/dc14-2709
M3 - Article
C2 - 26084345
AN - SCOPUS:84962440593
SN - 0149-5992
VL - 38
SP - 1456
EP - 1466
JO - Diabetes care
JF - Diabetes care
IS - 8
ER -