Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: The complex nature of genetic association through growth and development

Sovio, Ulla, Mook-Kanamori, Dennis O., Warrington, Nicole M., Lawrence, Robert, Briollais, Laurent, Palmer, Colin N. A., Cecil, Joanne, Sandling, Johanna K., Syvanen, Ann-Christin, Kaakinen, Marika, Beilin, Lawrie J., Millwood, Iona Y., Bennett, Amanda J., Laitinen, Jaana, Pouta, Anneli, Molitor, John, Smith, George Davey, Ben-Shlomo, Yoav, Jaddoe, Vincent W. V., Palmer, Lyle J., Pennell, Craig E., Cole, Tim J., McCarthy, Mark I., Jarvelin, Marjo-Riitta and Timpson, Nicholas J. (2011) Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: The complex nature of genetic association through growth and development. PLoS Genetics, 7 2: e1001307.1-e1001307.13. doi:10.1371/journal.pgen.1001307


Author Sovio, Ulla
Mook-Kanamori, Dennis O.
Warrington, Nicole M.
Lawrence, Robert
Briollais, Laurent
Palmer, Colin N. A.
Cecil, Joanne
Sandling, Johanna K.
Syvanen, Ann-Christin
Kaakinen, Marika
Beilin, Lawrie J.
Millwood, Iona Y.
Bennett, Amanda J.
Laitinen, Jaana
Pouta, Anneli
Molitor, John
Smith, George Davey
Ben-Shlomo, Yoav
Jaddoe, Vincent W. V.
Palmer, Lyle J.
Pennell, Craig E.
Cole, Tim J.
McCarthy, Mark I.
Jarvelin, Marjo-Riitta
Timpson, Nicholas J.
Title Association between common variation at the FTO locus and changes in body mass index from infancy to late childhood: The complex nature of genetic association through growth and development
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1001307
Open Access Status DOI
Volume 7
Issue 2
Start page e1001307.1
End page e1001307.13
Total pages 13
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Language eng
Subject 1311 Genetics
1312 Molecular Biology
1105 Dentistry
1306 Cancer Research
2716 Genetics (clinical)
Abstract An age-dependent association between variation at the FTO locus and BMI in children has been suggested. We meta-analyzed associations between the FTO locus (rs9939609) and BMI in samples, aged from early infancy to 13 years, from 8 cohorts of European ancestry. We found a positive association between additional minor (A) alleles and BMI from 5.5 years onwards, but an inverse association below age 2.5 years. Modelling median BMI curves for each genotype using the LMS method, we found that carriers of minor alleles showed lower BMI in infancy, earlier adiposity rebound (AR), and higher BMI later in childhood. Differences by allele were consistent with two independent processes: earlier AR equivalent to accelerating developmental age by 2.37% (95% CI 1.87, 2.87, p = 10-20) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10-23). We also fitted a linear mixed effects model to relate genotype to the BMI curve inflection points adiposity peak (AP) in infancy and AR. Carriage of two minor alleles at rs9939609 was associated with lower BMI at AP (-0.40% (95% CI: -0.74, -0.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (-4.72% (-5.81, -3.63), p = 10-17), supporting cross-sectional results. Overall, we confirm the expected association between variation at rs9939609 and BMI in childhood, but only after an inverse association between the same variant and BMI in infancy. Patterns are consistent with a shift on the developmental scale, which is reflected in association with the timing of AR rather than just a global increase in BMI. Results provide important information about longitudinal gene effects and about the role of FTO in adiposity. The associated shifts in developmental timing have clinical importance with respect to known relationships between AR and both later-life BMI and metabolic disease risk.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
 
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Created: Wed, 11 Jun 2014, 01:30:57 EST by Kylie Hengst on behalf of UQ Diamantina Institute