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Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth


Background:
Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity.

Methods and Findings:
Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an “obesity-risk-allele score” comprising the total number of risk alleles (range: 2–15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00–0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023–0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004–0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032–0.284) and with reduced risk of early infancy failure to thrive (odds ratio  = 0.92 per allele; 0.86–0.98; p = 0.009).

Conclusions:
The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort.

: Please see later in the article for the Editors' Summary


Vyšlo v časopise: Genetic Markers of Adult Obesity Risk Are Associated with Greater Early Infancy Weight Gain and Growth. PLoS Med 7(5): e32767. doi:10.1371/journal.pmed.1000284
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pmed.1000284

Souhrn

Background:
Genome-wide studies have identified several common genetic variants that are robustly associated with adult obesity risk. Exploration of these genotype associations in children may provide insights into the timing of weight changes leading to adult obesity.

Methods and Findings:
Children from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort were genotyped for ten genetic variants previously associated with adult BMI. Eight variants that showed individual associations with childhood BMI (in/near: FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5) were used to derive an “obesity-risk-allele score” comprising the total number of risk alleles (range: 2–15 alleles) in each child with complete genotype data (n = 7,146). Repeated measurements of weight, length/height, and body mass index from birth to age 11 years were expressed as standard deviation scores (SDS). Early infancy was defined as birth to age 6 weeks, and early infancy failure to thrive was defined as weight gain between below the 5th centile, adjusted for birth weight. The obesity-risk-allele score showed little association with birth weight (regression coefficient: 0.01 SDS per allele; 95% CI 0.00–0.02), but had an apparently much larger positive effect on early infancy weight gain (0.119 SDS/allele/year; 0.023–0.216) than on subsequent childhood weight gain (0.004 SDS/allele/year; 0.004–0.005). The obesity-risk-allele score was also positively associated with early infancy length gain (0.158 SDS/allele/year; 0.032–0.284) and with reduced risk of early infancy failure to thrive (odds ratio  = 0.92 per allele; 0.86–0.98; p = 0.009).

Conclusions:
The use of robust genetic markers identified greater early infancy gains in weight and length as being on the pathway to adult obesity risk in a contemporary birth cohort.

: Please see later in the article for the Editors' Summary


Zdroje

1. BundredP

KitchinerP

BuchanI

2001 Prevalence of overweight and obese children between 1989 and 1998: population based series of cross sectional studies. BMJ 322 326 328

2. DietzWH

1994 Critical periods in childhood for the development of obesity. American Journal of Clinical Nutrition 59 955 959

3. WhitakerRC

WrightJA

PepeMS

SeidelKD

DietzWH

1997 Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 337 869 873

4. FraylingTM

TimpsonNJ

WeedonMN

ZegginiE

FreathyRM

2007 A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316 889 894

5. LoosRJ

LindgrenCM

LiS

WheelerE

ZhaoJH

2008 Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40 768 775

6. WillerCJ

SpeliotesEK

LoosRJ

LiS

LindgrenCM

2009 Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 41 25 34

7. ThorleifssonG

WaltersGB

GudbjartssonDF

SteinthorsdottirV

SulemP

2009 Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 41 18 24

8. CecilJE

TavendaleR

WattP

HetheringtonMM

PalmerCN

2008 An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med 359 2558 2566

9. GrantSF

BradfieldJP

ZhangH

WangK

KimCE

2009 Investigation of the Locus Near MC4R With Childhood Obesity in Americans of European and African Ancestry. Obesity (Silver Spring)

10. GoldingJ

PembreyM

JonesR

2001 ALSPAC–the Avon Longitudinal Study of Parents and Children. I. Study methodology. Paediatr Perinat Epidemiol 15 74 87

11. ColeTJ

FreemanJV

PreeceMA

1995 Body mass index reference curves for the UK, 1990. Arch Dis Child 73 25 29

12. FreemanJV

ColeTJ

ChinnS

JonesPR

WhiteEM

1995 Cross sectional stature and weight reference curves for the UK, 1990. Archives of Disease in Childhood 73 17 24

13. ColeTJ

BellizziMC

FlegalKM

DietzWH

2000 Establishing a standard definition for child overweight and obesity worldwide: international survey. Bmj 320 1240 1243

14. WellsJC

ColeTJ

2002 Adjustment of fat-free mass and fat mass for height in children aged 8 y. Int J Obes Relat Metab Disord 26 947 952

15. ColeTJ

1995 Conditional reference charts to assess weight gain in British infants. Arch Dis Child 73 8 16

16. DrewettR

BlairP

EmmettP

EmondA

2004 Failure to thrive in the term and preterm infants of mothers depressed in the postnatal period: a population-based birth cohort study. J Child Psychol Psychiatry 45 359 366

17. Stata. Corp 2007 Stata Statistical Software: Release 10. College Station, TX StataCorp LP

18. MeyreD

DelplanqueJ

ChevreJC

LecoeurC

LobbensS

2009 Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41 157 159

19. KarlbergJ

1987 On the modelling of human growth. Stat Med 6 185 192

20. OngKK

LoosRJ

2006 Rapid infancy weight gain and subsequent obesity: systematic reviews and hopeful suggestions. Acta Paediatr 95 904 908

21. BairdJ

FisherD

LucasP

KleijnenJ

RobertsH

2005 Being big or growing fast: systematic review of size and growth in infancy and later obesity. BMJ 331 929

22. FallCH

SachdevHS

OsmondC

LakshmyR

BiswasSD

2008 Adult metabolic syndrome and impaired glucose tolerance are associated with different patterns of BMI gain during infancy: Data from the New Delhi Birth Cohort. Diabetes Care 31 2349 2356

23. StettlerN

2007 Commentary: Growing up optimally in societies undergoing the nutritional transition, public health and research challenges. Int J Epidemiol 36 558 559

24. OngKK

PreeceMA

EmmettPM

AhmedML

DungerDB

2002 Size at birth and early childhood growth in relation to maternal smoking, parity and infant breast-feeding: longitudinal birth cohort study and analysis. Pediatric Research 52 863 867

25. JolleyCD

2003 Failure to thrive. Curr Probl Pediatr Adolesc Health Care 33 183 206

26. SkuseDH

1985 Non-organic failure to thrive: a reappraisal. Arch Dis Child 60 173 178

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PLOS Medicine


2010 Číslo 5
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