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dc.contributor.authorSovio, Ulla
dc.contributor.authorMook-Kanamori, Dennis O.
dc.contributor.authorWarrington, Nicole M.
dc.contributor.authorLawrence, Robert
dc.contributor.authorBriollais, Laurent
dc.contributor.authorPalmer, Colin N.A.
dc.contributor.authorCecil, Joanne Elizabeth
dc.contributor.authorSandling, Johanna
dc.contributor.authorSyvänen, Ann-Christine
dc.contributor.authorKaakinen, Marika
dc.contributor.authorBeilin, Lawrie
dc.contributor.authorMillwood, Iona
dc.contributor.authorBennett, Amanda
dc.contributor.authorLaitinen, Jaana
dc.contributor.authorPouta, Anneli
dc.contributor.authorMolitor, John
dc.contributor.authorDavey Smith, George
dc.contributor.authorBen-Shlomo, Yoav
dc.contributor.authorJaddoe, Vincent
dc.contributor.authorPalmer, Lyle
dc.contributor.authorPennell, Craig
dc.contributor.authorCole, Tim
dc.contributor.authorMcCarthy, Mark
dc.contributor.authorJärvelin, Marjo-Riitta
dc.contributor.authorTimpson, Nicholas
dc.date.accessioned2012-02-16T15:31:03Z
dc.date.available2012-02-16T15:31:03Z
dc.date.issued2011
dc.identifier.citationSovio , U , Mook-Kanamori , D O , Warrington , N M , Lawrence , R , Briollais , L , Palmer , C N A , Cecil , J E , Sandling , J , Syvänen , A-C , Kaakinen , M , Beilin , L , Millwood , I , Bennett , A , Laitinen , J , Pouta , A , Molitor , J , Davey Smith , G , Ben-Shlomo , Y , Jaddoe , V , Palmer , L , Pennell , C , Cole , T , McCarthy , M , Järvelin , M-R & Timpson , N 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 , vol. 7 , no. 2 , e1001307 . https://doi.org/10.1371/journal.pgen.1001307en
dc.identifier.issn1553-7390
dc.identifier.otherPURE: 6214941
dc.identifier.otherPURE UUID: 9d0c5b67-db40-455a-bacb-193ad39042d5
dc.identifier.otherScopus: 79952262429
dc.identifier.otherWOS: 000287697300022
dc.identifier.otherORCID: /0000-0003-4779-6037/work/60196868
dc.identifier.urihttp://hdl.handle.net/10023/2322
dc.description.abstractAn age-dependent association between variation at the FTO locus and BMI in children has been suggested. We metaanalyzed 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 = 10220) per A allele and a positive age by genotype interaction such that BMI increased faster with age (p = 10223). 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 (20.40% (95% CI: 20.74, 20.06), p = 0.02), higher BMI at AR (0.93% (95% CI: 0.22, 1.64), p = 0.01), and earlier AR (24.72% (25.81, 23.63), p = 10217), 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.
dc.format.extent13
dc.language.isoeng
dc.relation.ispartofPLoS Geneticsen
dc.rights© 2011 Sovio et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en
dc.subjectQH426 Geneticsen
dc.subject.lccQH426en
dc.titleAssociation 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 developmenten
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Health Psychologyen
dc.identifier.doihttps://doi.org/10.1371/journal.pgen.1001307
dc.description.statusPeer revieweden


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