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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
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نویسنده
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sovio u. ,mook-kanamori d.o. ,warrington n.m. ,lawrence r. ,briollais l. ,palmer c.n.a. ,cecil j. ,sandling j.k. ,syvänen a.-c. ,kaakinen m. ,beilin l.j. ,millwood i.y. ,bennett a.j. ,laitinen j. ,pouta a. ,molitor j. ,smith g.d. ,ben-shlomo y. ,jaddoe v.w.v. ,palmer l.j. ,pennell c.e. ,cole t.j. ,mccarthy m.i. ,järvelin m.-r. ,timpson n.j.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 2
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چکیده
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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. © 2011 sovio et al.
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آدرس
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department of epidemiology and biostatistics,imperial college,london,united kingdom,the london school of hygiene and tropical medicine,london, United Kingdom, department of pediatrics,erasmus medical center,rotterdam,netherlands,department of epidemiology,erasmus medical center,rotterdam,netherlands,the generation r study,erasmus medical center,rotterdam, Netherlands, school of women's and infants' health,the university of western australia,perth, Australia, centre for genetic epidemiology and biostatistics,the university of western australia,perth, Australia, samuel lunenfeld research institute,mount sinai hospital,university of toronto,toronto, Canada, biomedical research institute,university of dundee,ninewells hospital and medical school,dundee, United Kingdom, bute medical school,university of st andrews,st andrews, United Kingdom, molecular medicine,department of medical sciences,uppsala university,uppsala, Sweden, molecular medicine,department of medical sciences,uppsala university,uppsala, Sweden, institute of health sciences,university of oulu,oulu,finland,biocenter oulu,university of oulu,oulu, Finland, school of medicine and pharmacology,the university of western australia,perth, Australia, department of epidemiology and biostatistics,imperial college,london,united kingdom,clinical trial service unit and epidemiological studies unit,university of oxford,oxford, United Kingdom, oxford centre for diabetes,endocrinology and metabolism,university of oxford,oxford, United Kingdom, finnish institute of occupational health,oulu, Finland, department of lifecourse and services,national institute of health and welfare,oulu, Finland, department of epidemiology and biostatistics,imperial college,london, United Kingdom, mrc centre for causal analyses in translational epidemiology,university of bristol,bristol,united kingdom,department of social medicine,university of bristol,bristol, United Kingdom, department of social medicine,university of bristol,bristol, United Kingdom, department of pediatrics,erasmus medical center,rotterdam,netherlands,department of epidemiology,erasmus medical center,rotterdam,netherlands,the generation r study,erasmus medical center,rotterdam, Netherlands, ontario institute for cancer research,samuel lunenfeld research institute,toronto, Canada, school of women's and infants' health,the university of western australia,perth, Australia, mrc centre of epidemiology for child health,ucl institute of child health,london, United Kingdom, oxford centre for diabetes,endocrinology and metabolism,university of oxford,oxford,united kingdom,wellcome trust centre for human genetics,university of oxford,oxford,united kingdom,oxford nihr biomedical research centre,churchill hospital,oxford, United Kingdom, department of epidemiology and biostatistics,imperial college,london,united kingdom,institute of health sciences,university of oulu,oulu,finland,biocenter oulu,university of oulu,oulu,finland,department of lifecourse and services,national institute of health and welfare,oulu, Finland, mrc centre for causal analyses in translational epidemiology,university of bristol,bristol,united kingdom,department of social medicine,university of bristol,bristol, United Kingdom
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