Association between genetic obesity susceptibility and mother-reported eating behaviour in children up to 5 years.

TLDR: Many genetic polymorphisms identified by genome‐wide association studies for adult body mass index (BMI) have been suggested to regulate food intake.

Abstract: Background Many genetic polymorphisms identified by genome-wide association studies for adult body mass index (BMI) have been suggested to regulate food intake. Objective The objective was to study the associations between a genetic obesity risk score, appetitive traits, and growth of children up to age 5 years, with a longitudinal design. Methods In 1142 children from the Etude des Determinants pre et post natals de la sante de l'ENfant (EDEN) birth cohort, a combined obesity risk-allele score (BMI genetic risk score [GRS]) was related to appetitive traits (energy intake up to 12 mo, a single item on appetite from 4 mo to 3 y, a validated appetite score at 5 y) using Poisson regressions with robust standard errors. The potential mediation of appetitive traits on the association between BMI-GRS and growth was assessed by the Sobel test. Results Children with a high BMI-GRS were more likely to have high energy intake at 1 year and high appetite at 2 and 5 years. High energy intake in infancy and high appetite from 1 year were related to higher subsequent BMI. High 2-year appetite seemed to partially mediate the associations between BMI-GRS and BMI from 2 to 5 years (all P ≤ 0.05). Conclusions Genetic susceptibility to childhood obesity seems to be partially explained by appetitive traits in infancy, followed by an early childhood rise in BMI.

Figures

Figure 2. Association between the obesity risk-allele score and child’s WHO z-scores from 2 to 5 years

Figure 1. Association between obesity risk-allele score and child’s eating behaviour, up to 5 years

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Association between genetic obesity susceptibility and
mother-reported eating behavior in children up to 5
years
Blandine de Lauzon-Guillain, Yves Akoli Koudou, Jérémie Botton, Anne
Forhan, Sophie Carles, Véronique Pelloux, Karine Clément, Ken K. Ong,
Marie Aline Charles, Barbara Heude
To cite this version:
Blandine de Lauzon-Guillain, Yves Akoli Koudou, Jérémie Botton, Anne Forhan, Sophie Carles, et al..
Association between genetic obesity susceptibility and mother-reported eating behavior in children up
to 5 years: genetic obesity risk and child’s eating behavior. International Journal of Pediatric Obesity,
Taylor & Francis, 2019, 14 (5), pp.e12496. �10.1111/ijpo.12496�. �inserm-02093066�

1
1
Association between genetic obesity susceptibility and mother-reported
eating behavior in children up to 5 years
Blandine de Lauzon-Guillain, PhD
1,2,8
, Yves Akoli Koudou, MSc
1
, Jérémie Botton, PhD
1,3
,
Anne Forhan, MSc
1,2
, Sophie Carles, PhD
1
, Véronique Pelloux, PhD
4,5,6
, Karine Clément,
PhD
4,5,6
, Ken K. Ong, FRCPCH
7
, Marie Aline Charles, MD, PhD
1,2
, Barbara Heude, PhD
1,2
;
on behalf of the EDEN Mother-Child Cohort Study Group*
* Members of the EDEN Mother-Child Cohort Study Group: I. Annesi-Maesano, JY.
Bernard, J. Botton, M.A. Charles, P. Dargent-Molina, B. de Lauzon-Guillain, P. Ducimetière,
M. de Agostini, B. Foliguet, A. Forhan, X. Fritel, A. Germa, V. Goua, R. Hankard, B. Heude,
M. Kaminski, B. Larroque†, N. Lelong, J. Lepeule, G. Magnin, L. Marchand, C. Nabet, F.
Pierre, R. Slama, M.J. Saurel-Cubizolles, M. Schweitzer, O. Thiebaugeorges.
Affiliations
1
INSERM, UMR1153 Epidemiology and Biostatistics Sorbonne Paris Cité Center, Early
ORigin of the Child’s Health and Development Team (ORCHAD), Paris, France
2
Paris Descartes University, France
3
Univ. Paris-Sud, Université Paris-Saclay, Faculty of Pharmacy, F-92296, Châtenay-
Malabry, France;
4
Institute of Cardiometabolism and Nutrition, ICAN, F-75013, Paris, France;
5
INSERM, UMRS 1166, Nutriomic team 6, Paris, F-75013 France;
6
Sorbonne Universités, UPMC Université Paris 06, UMRS1166, Paris, F-75013 France;
7
Medical Research Council Epidemiology Unit & Department of Paediatrics, University of
Cambridge, Addenbrooke’s Hospital, Cambridge, England
8
INRA, U1125 Epidemiology and Biostatistics Sorbonne Paris Cité Center (CRESS), Early
ORigin of the Child’s Health and Development Team (ORCHAD), Paris, F-75014 France.

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2
PubMed indexing.
de Lauzon-Guillain, Koudou, Botton, Forhan, Carles, Pelloux, Clément, Ong, Charles, Heude;
on behalf of the EDEN Mother-Child Cohort Study Group
Running head
genetic obesity risk and child’s eating behavior
Keywords
obesity, genetic, eating behaviour, growth, birth cohort, childhood
Corresponding author
de Lauzon-Guillain Blandine
INSERM CRESS – Eq6 ORCHAD
16 av. Paul Vaillant Couturier, 94807 Villejuif Cedex, FRANCE
Tel: +33145595019; Fax: +33147269454; E-mail: blandine.delauzon@inserm.fr
Abbreviations
BMI-GRS: combined obesity risk-allele score
SNP: single-nucleotide polymorphisms

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Abstract
1
Background. Many genetic polymorphisms identified by genome wide association studies
2
for adult BMI have been suggested to regulate food intake.
3
Objective. The objective was to study the associations between a genetic obesity risk score,
4
appetitive traits and growth of children up to age 5 years, with a longitudinal design.
5
Methods. In 1,142 children from the EDEN birth cohort, a combined obesity risk-allele score
6
(BMI-GRS) was related to appetitive traits (energy intake up to 12 months, a single item on
7
appetite from 4 months to 3 years, a validated appetite score at 5 years) using Poisson
8
regressions with robust standard errors. The potential mediation of appetitive traits on the
9
association between BMI-GRS and growth was assessed by the Sobel test.
10
Results. Children with a high BMI-GRS were more likely to have high energy intake at 1
11
year and high appetite at 2 and 5 years. High energy intake in infancy and high appetite from
12
1 year were related to higher subsequent BMI. High 2-y appetite seemed to partially mediate
13
the associations between BMI-GRS and BMI from 2 to 5 years (all p<=0.05).
14
Conclusions. Genetic susceptibility to childhood obesity seems to be partially explained by
15
appetitive traits in infancy, followed by an early childhood rise in BMI.
16
17

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Introduction
18
Genome-wide-association studies (GWAs) have identified several genes associated with an
19
increased risk of obesity (1, 2). Time has now come to take advantage of these major findings
20
in order to better understand the mechanisms of lifecourse obesity development from infancy
21
to adulthood. Many birth cohorts have shown that scores of genetic susceptibility to obesity
22
are associated with early growth, as early as 2 years in some of them, but not with foetal
23
growth (3, 4, 5, 6).
24
A great part of the genes implicated by GWAs, and especially those from monogenic studies
25
on severe childhood or early onset obesity, are purportedly involved in the central regulation
26
of food intake (7). Furthermore, the genetic component of eating behavior has clearly been
27
established through heritability studies, in adults (8) and also in children (9, 10). Eating
28
behavior even in infancy may influence later adiposity development (11), which raises the
29
question whether the association between the genetic score and adiposity is mediated by
30
eating behaviour in childhood. Cross-sectional studies, conducted among 8-11 years children,
31
have already shown that increased BMI of children homozygous for the at-risk allele of a
32
FTO SNP may be partially mediated by appetitive traits (12, 13). Similarly, a cross-sectional
33
analysis of the Twins Early Development Study highlighted that satiety responsiveness
34
partially mediated the association between a polygenic risk score and adiposity in children
35
aged 8-11 years(14). However, such a cross-sectional design is insufficient to establish a
36
causal pathway. More recently, this causal pathway has been tested longitudinally within a
37
Norwegian cohort following children from the age of 4 years to the age of 8 years (15). In that
38
study, higher genetic risk for obesity was associated with appetitive traits at 6 years, but these
39
appetitive traits were not related to BMI gain up to 8 years. As a previous study has shown
40
that appetitive traits assessed at age 3 months predicted weight at 9 months, it would be
41
important to test the potential mediating effect of infant or toddler’s appetitive traits on
42

Frequently asked questions

Q1. What contributions have the authors mentioned in the paper "Association between genetic obesity susceptibility and mother-reported eating behavior in children up to 5 years" ?

HAL this paper is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. 

Q2. What other traits were found to be related to weight in the Gemini study?

In that study, the possibility of reverse causality was suggested by the 247 observation that weight at 9 months was also related to appetitive traits in toddlers, with 248 stronger association for food responsiveness, satiety responsiveness and general appetite. 

Q3. how many risk alleles were calculated for each participant?

88Combined obesity risk-allele scores, indicating genetic susceptibility to obesity, were 89 calculated for each participant as the sum of risk alleles (0, 1 or 2 at each locus) associated 90 with higher BMI across the 16 SNP loci. 

Q4. How was the weight of the weighted BMI-GRS related to eating behaviours?

Among all children, BMI-GRS was positively related 184 to maternal perception of high appetite between 8 months and 5 years, although not 185 significant in the first year or at 3 years. 

Q5. How many genes were imputed to the infants with missing genotype data?

To minimize dropout 91 due to missing genotype data, infants with missing genotype data at 4 (25%) or fewer loci 92 were imputed with the mean number of susceptibility alleles in their cohort for each locus. 

Q6. What was the effect of the Sobel test on the z-scores?

The Sobel test for mediation was significant but the 212mediation was only partial with a mediation ratio decreasing with time from 47% for 2-y BMI 213 z-score (p=0.03) and 35% for 3-y BMI z-score (p=0.03) to 28% for 4-y BMI z-score (p=0.05) 214 and 24% for 5-y BMI (p=0.05). 

Q7. What was the effect of the Sobel test on the obesity score?

In their study, the score of genetic predisposition to develop obesity was association with a 218 higher risk of high energy intake at 1 year, and high parental-perceived appetite at 2 and 5 219 years. 

Q8. How many SNPs were identified as having associations with BMI in adults?

78 Among the 32 loci identified by Speliotes et al. as having genome-wide significant 79 associations with BMI in adults (2), the authors considered in the present study the 16 SNPs also 80 showing associations with childhood BMI either in that original report (2) or in subsequent 81 data (4); they lie in or near NRXN3 (rs10146997), SLC39A8 (rs13107325), TNNI3K 82 (rs1514175), PTBP2 (rs1555543), MC4R (rs17782313), FLJ35779 (rs2112347), NEGR1 83 (rs2568958), RPL27A (rs4929949), TMEM18 (rs6548238), RBJ/POMC (rs713586), CADM2 84 (rs7640855), TRA2B/ETV5 (rs7647305), BDNF (rs925946), TFAP2B (rs987237), FTO 85 (rs9941349), and ZNF608 (rs4836133). 

Q9. How many pregnant women were recruited in 2002?

In brief, 2002 pregnant women were recruited from 2003 to 2006 in 54 two French university hospitals, before 24 weeks of amenorrhea. 

Q10. How was the weight-for-age z score related to the child’s weight?

High energy intake at 12 months was positively related to 193 weight-for-age z-score from 3 to 5 years but was not related to length/ height-for-age or BMI-194 for-age z-scores. 

Q11. What is the effect of the Sobel test on the BMI-GRS?

237If evidence of a mediating effect of appetitive traits on the association between the BMI-GRS 238 and BMI remains scarce, many studies examined the influence of appetitive traits on BMI. 

Q12. What was the sensitivity test for the WHO z-score?

To test for mediation, the linear regression of genetic risk score on each 162 WHO z-score was adjusted for the considered eating behaviour. 

Q13. What is the role of the GWAs in the regulation of food intake?

24 A great part of the genes implicated by GWAs, and especially those from monogenic studies 25 on severe childhood or early onset obesity, are purportedly involved in the central regulation 26 of food intake (7).