Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents

• Published in: International Journal of Obesity Vol. 43; no. 10; pp. 2007 - 2016
• Main Authors: Viitasalo, Anna, Schnurr, Theresia M., Pitkänen, Niina, Hollensted, Mette, Nielsen, Tenna R. H., Pahkala, Katja, Lintu, Niina, Lind, Mads V., Atalay, Mustafa, Frithioff-Bøjsøe, Christine, Fonvig, Cilius E., Grarup, Niels, Kähönen, Mika, Larnkjaer, Anni, Pedersen, Oluf, Holm, Jens-Christian, Michaelsen, Kim F., Lakka, Timo A., Lehtimäki, Terho, Raitakari, Olli, Hansen, Torben, Kilpeläinen, Tuomas O.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.10.2019; Nature Publishing Group
• Subjects: 45/43; 631/208; 692/308/174; 692/499; Adipose Tissue; Adolescent; Adolescents; Alleles; Analysis; Body fat; Body Mass Index; Body size; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - genetics; Cardiovascular Diseases - physiopathology; Child; Child, Preschool; Children; Cholesterol; Denmark - epidemiology; Dyslipidemia; Epidemiology; Female; Finland - epidemiology; Genetic aspects; Genetic Predisposition to Disease - epidemiology; Genetic susceptibility; Health Promotion and Disease Prevention; Health risks; High density lipoprotein; Hip; Humans; Hypertension; Insulin; Internal Medicine; Lipids; Longitudinal Studies; Male; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic Diseases - epidemiology; Metabolic Diseases - genetics; Metabolic Diseases - physiopathology; Obesity; Obesity in adolescence; Obesity in children; Pediatric Obesity - epidemiology; Pediatric Obesity - genetics; Pediatric Obesity - physiopathology; Puberty; Public Health; Risk factors; Sensitivity; Systematic review; Teenagers; Triglycerides; Waist Circumference; Waist-Hip Ratio; Whites; Denmark; Finland
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/s41366-019-0414-0

Background Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. Methods We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist–hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3–18 years. Results The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P  = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P  = 0.031), yet improved body fat distribution (lower WHR adjBMI beta = −0.014 SD/allele, SE = 0.006, P  = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P  = 0.002; lower triglycerides: beta = −0.011 SD/allele, SE = 0.003, P  = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01–1.13, P  = 0.012, n  = 536). Conclusions Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.