Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 May 25;7(5):e1000284.
doi: 10.1371/journal.pmed.1000284.

Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth

Cathy E Elks  1 , Ruth J F Loos, Stephen J Sharp, Claudia Langenberg, Susan M Ring, Nicholas J Timpson, Andrew R Ness, George Davey Smith, David B Dunger, Nicholas J Wareham, Ken K Ong
Affiliations

Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth

Cathy E Elks et al. PLoS Med. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

George Davey Smith is on the Editorial Board of PLoS Medicine.

Figures

Figure 1
Figure 1. Distribution of the obesity-risk-allele score in ALSPAC children.
The risk-allele score comprises genotypes at eight loci (FTO, MC4R, TMEM18, GNPDA2, KCTD15, NEGR1, BDNF, and ETV5). Error bars (and 2nd y-axis) display the mean (±95% CI) BMI SDS at age 9 y for each risk score value.
Figure 2
Figure 2. Longitudinal associations between the obesity-risk-allele score and (A) weight SDS, (B) length/height SDS, and (C) BMI SDS.
Regression coefficients ±95% CI are shown from linear regression models (adjusted for sex and precise age at measurement) according to age at measurement between birth and 11 y.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Bundred P, Kitchiner P, Buchan I. Prevalence of overweight and obese children between 1989 and 1998: population based series of cross sectional studies. BMJ. 2001;322:326–328. - PMC - PubMed
    1. Dietz WH. Critical periods in childhood for the development of obesity. American Journal of Clinical Nutrition. 1994;59:955–959. - PubMed
    1. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH. Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med. 1997;337:869–873. - PubMed
    1. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316:889–894. - PMC - PubMed
    1. Loos RJ, Lindgren CM, Li S, Wheeler E, Zhao JH, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40:768–775. - PMC - PubMed

Publication types

Substances