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

Anna Viitasalo; Theresia Maria Schnurr; Niina Pitkänen; Mette Hollensted; Tenna R H Nielsen; Katja Pahkala; Niina Lintu; Mads Vendelbo Lind; Mustafa Atalay; Christine Frithioff-Bøjsøe; Cilius Esmann Fonvig; Niels Grarup; Mika Kähönen; Anni Larnkjær; Oluf Borbye Pedersen; Jens-Christian Holm; Kim F. Michaelsen; Timo A Lakka; Terho Lehtimäki; Olli Raitakari; Torben Hansen; Tuomas Oskari Kilpeläinen

doi:10.1038/s41366-019-0414-0

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

Anna Viitasalo^*, Theresia Maria Schnurr, Niina Pitkänen, Mette Hollensted, Tenna R H Nielsen, Katja Pahkala, Niina Lintu, Mads Vendelbo Lind, Mustafa Atalay, Christine Frithioff-Bøjsøe, Cilius Esmann Fonvig, Niels Grarup, Mika Kähönen, Anni Larnkjær, Oluf Borbye Pedersen, Jens-Christian Holm, Kim F. Michaelsen, Timo A Lakka, Terho Lehtimäki, Olli RaitakariTorben Hansen, Tuomas Oskari Kilpeläinen

^*Corresponding author for this work

4 Citations (Scopus)

Abstract

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.

Original language	English
Journal	International Journal of Obesity
Volume	43
Pages (from-to)	2007-2016
Number of pages	10
ISSN	0307-0565
DOIs	https://doi.org/10.1038/s41366-019-0414-0
Publication status	Published - 1 Oct 2019

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Viitasalo, A., Schnurr, T. M., Pitkänen, N., Hollensted, M., Nielsen, T. R. H., Pahkala, K., Lintu, N., Lind, M. V., Atalay, M., Frithioff-Bøjsøe, C., Fonvig, C. E., Grarup, N., Kähönen, M., Larnkjær, A., Pedersen, O. B., Holm, J.-C., Michaelsen, K. F., Lakka, T. A., Lehtimäki, T., ... Kilpeläinen, T. O. (2019). Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents. International Journal of Obesity, 43, 2007-2016. https://doi.org/10.1038/s41366-019-0414-0

Viitasalo, A, Schnurr, TM, Pitkänen, N, Hollensted, M, Nielsen, TRH, Pahkala, K, Lintu, N, Lind, MV, Atalay, M, Frithioff-Bøjsøe, C, Fonvig, CE, Grarup, N, Kähönen, M, Larnkjær, A , Pedersen, OB , Holm, J-C , Michaelsen, KF, Lakka, TA, Lehtimäki, T, Raitakari, O, Hansen, T & Kilpeläinen, TO 2019, 'Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents', International Journal of Obesity, vol. 43, pp. 2007-2016. https://doi.org/10.1038/s41366-019-0414-0

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title = "Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents",

abstract = "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 WHRadjBMI 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.",

author = "Anna Viitasalo and Schnurr, {Theresia Maria} and Niina Pitk{\"a}nen and Mette Hollensted and Nielsen, {Tenna R H} and Katja Pahkala and Niina Lintu and Lind, {Mads Vendelbo} and Mustafa Atalay and Christine Frithioff-B{\o}js{\o}e and Fonvig, {Cilius Esmann} and Niels Grarup and Mika K{\"a}h{\"o}nen and Anni Larnkj{\ae}r and Pedersen, {Oluf Borbye} and Jens-Christian Holm and Michaelsen, {Kim F.} and Lakka, {Timo A} and Terho Lehtim{\"a}ki and Olli Raitakari and Torben Hansen and Kilpel{\"a}inen, {Tuomas Oskari}",

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doi = "10.1038/s41366-019-0414-0",

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T1 - Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents

AU - Viitasalo, Anna

AU - Schnurr, Theresia Maria

AU - Pitkänen, Niina

AU - Hollensted, Mette

AU - Nielsen, Tenna R H

AU - Pahkala, Katja

AU - Lintu, Niina

AU - Lind, Mads Vendelbo

AU - Atalay, Mustafa

AU - Frithioff-Bøjsøe, Christine

AU - Fonvig, Cilius Esmann

AU - Grarup, Niels

AU - Kähönen, Mika

AU - Larnkjær, Anni

AU - Pedersen, Oluf Borbye

AU - Holm, Jens-Christian

AU - Michaelsen, Kim F.

AU - Lakka, Timo A

AU - Lehtimäki, Terho

AU - Raitakari, Olli

AU - Hansen, Torben

AU - Kilpeläinen, Tuomas Oskari

N1 - CURIS 2019 NEXS 228

PY - 2019/10/1

Y1 - 2019/10/1

N2 - 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 WHRadjBMI 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.

AB - 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 WHRadjBMI 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.

U2 - 10.1038/s41366-019-0414-0

DO - 10.1038/s41366-019-0414-0

M3 - Journal article

C2 - 31332278

SN - 0307-0565

VL - 43

SP - 2007

EP - 2016

JO - International Journal of Obesity

JF - International Journal of Obesity

ER -

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

Abstract

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