4.6 Article

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

期刊

PLOS GENETICS
卷 7, 期 2, 页码 -

出版社

PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pgen.1001307

关键词

-

资金

  1. ALSPAC - The UK Medical Research Council
  2. Wellcome Trust [GR069224]
  3. UK Department of Health
  4. British Lung Foundation
  5. University of Bristol, Cancer Research UK
  6. Medical Research Council [G07000961]
  7. Erasmus Medical Center, Rotterdam
  8. Erasmus University Rotterdam
  9. Netherlands Organization for Health Research and Development (ZonMw)
  10. Swedish Research Council for Medicine
  11. Academy of Finland [104781]
  12. Medical Research Council, UK [G0500539]
  13. University of Western Australia (UWA)
  14. Raine Medical Research Foundation
  15. UWA Faculty of Medicine, Dentistry, and Health Sciences
  16. Telethon Institute for Child Health Research and Women and Infants Research Foundation
  17. National Health and Medical Research Council of Australia [ID 403981, ID 003209]
  18. Canadian Institutes of Health Research [MOP-82893]
  19. Biotechnology and Biological Sciences Research Council [D13460]
  20. MRC Centre for Causal Analyses in Translational Epidemiology [G0600705]
  21. Netherlands Organization for Health Research (ZonMw) [90700303]
  22. Academy of Finland (Center of Excellence in Complex Disease Genetics) [104781, 120315]
  23. University Hospital Oulu, Biocenter, University of Oulu, Finland
  24. European Commission [QLG1-CT-2000-01643]
  25. NHLBI [5R01HL087679-02, 1RL1MH083268-01]
  26. NIH/NIMH [5R01MH63706:02]
  27. ENGAGE project [HEALTH-F4-2007-201413]
  28. Medical Research Council, UK (Salve/PrevMetSyn)
  29. British Heart Foundation
  30. Diabetes UK
  31. MRC [G0600705, G0700961] Funding Source: UKRI
  32. Medical Research Council [G0600705, G0700961, G0801056B, G9815508] Funding Source: researchfish

向作者/读者索取更多资源

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 = 10 223). 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 = 10 217), 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据