期刊
AMERICAN JOURNAL OF CLINICAL NUTRITION
卷 110, 期 5, 页码 1079-1087出版社
ELSEVIER SCIENCE INC
DOI: 10.1093/ajcn/nqz187
关键词
abdominal adiposity; children; waist-to-hip ratio; cardiovascular disease risk; cardiometabolic risk; Mendelian randomization; meta-analysis; ALSPAC
资金
- European Union (EU)'s Horizon 2020 research and innovation program under Marie Sklodowska-Curie grant [796143]
- Orion Research Foundation
- Emil Aaltonen Foundation
- Danish Council for Independent Research [DFF-6110-00183]
- Novo Nordisk Foundation [NNF17OC0026848, NNF18CC0034900, NNF15OC0016544]
- UK Medical Research Council
- Wellcome Trust [102215/2/13/2, 086676/Z/08/Z]
- University of Bristol
- Academy of Finland [286284, 134309, 126925, 121584, 124282, 129378, 117787, 41071, 206374, 294834, 251360, 275595]
- Social Insurance Institution of Finland
- Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere
- Turku University Hospitals [X51001]
- Juho Vainio Foundation
- Paavo Nurmi Foundation
- Finnish Foundation for Cardiovascular Research
- Finnish Cultural Foundation
- Sigrid Juselius Foundation
- Tampere Tuberculosis Foundation
- Yrjo Jahnsson Foundation
- Signe and Ane Gyllenberg Foundation
- Diabetes Research Foundation of the Finnish Diabetes Association
- EU Horizon 2020 [755320]
- European Research Council [742927]
- Tampere University Hospital Supporting Foundation
- Danish Childhood Obesity Biobank [NCT00928473]
- Danish Innovation Foundation [0603-00484B, 0603-00457B]
- Region Zealand Health
- Medical Research Foundation
- Finnish Diabetes Research Foundation
- Finnish Ministry of Education and Culture
- Special Governmental Grants for Health Sciences Research
- University of Turku Foundation
- Ministry of Social Affairs and Health of Finland
- Ministry of Education and Culture of Finland
- Finnish Innovation Fund Sitra
- Foundation for Paediatric Research
- Paulo Foundation
- Diabetes Research Foundation
- Research Committee of the Kuopio University Hospital Catchment Area (State Research Funding)
- Kuopio University Hospital (EVO) [5031343]
- city of Kuopio
- Danish Directorate for Food, Fisheries, and Agri Business as part of the Complementary and young child feeding (CYCF)-impact on short-and long-term development and health project
- Aase and Ejnar Danielsens Foundation
- Augustinus Foundation
- research program Governing Obesity by the University of Copenhagen Excellence Program for Interdisciplinary Research
- Turku University Hospital
- 23andMe
- MRC [MC_PC_19009] Funding Source: UKRI
- Wellcome Trust [086676/Z/08/Z] Funding Source: Wellcome Trust
- Marie Curie Actions (MSCA) [796143] Funding Source: Marie Curie Actions (MSCA)
Background: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. Objective: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization. Methods: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y. Results: WHRadjBMI GRS was associated with higher WHRadjBMI (beta = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 x 10(-15)) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: beta = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: beta = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: beta = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (beta = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (beta = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal. Conclusions: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.
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