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Human Genetics

, Volume 128, Issue 6, pp 589–596 | Cite as

FTO influences on longitudinal BMI over childhood and adulthood and modulation on relationship between birth weight and longitudinal BMI

  • Hao Mei
  • Wei Chen
  • Sathanur R. Srinivasan
  • Fan Jiang
  • Nicholas Schork
  • Sarah Murray
  • Erin Smith
  • Joanne D. So
  • Gerald S. BerensonEmail author
Original Investigation

Abstract

SNP rs9939609 within the fat mass and obesity associated gene (FTO) is strongly associated with adult body mass index (BMI). However, influences of FTO on longitudinal BMI change from childhood to adulthood have not been examined. Knowledge is limited on FTO, modulating the association between birth weight and longitudinal change of BMI. This longitudinal study examined SNPs of FTO in 658 white subjects from childhood (3–17 years) to adulthood (18–45 years). No significant associations of FTO SNPs with either birth weight or longitudinal BMI over childhood were noted after multiple-test adjustment. However, three SNPs (rs9939609, rs17820875 and rs860713) with different inheritance patterns were identified to be associated with longitudinal BMI over adulthood after Bonferroni adjustment (P = 5.3 × 10−5, 2.0 × 10−4 and 0.001). In addition, interactions were discovered between birth weight and SNPs of rs17820875 (P = 0.001) and rs860713 (0.002). A negative association between birth weight and adult BMI were found in risk genotype AG of rs17820875 and GG of rs860713 in contrast to positive associations in other genotypes. These findings led to the conclusion that lower birth weight predisposes to higher adult BMI depending on FTO risk genotypes. Our studies underscore the importance of FTO influences on obesity and provide insights into the evolution of the long-term burden of obesity.

Keywords

Body Mass Index Birth Weight Minor Allele Frequency Risk Genotype Adult Body Mass Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Abelson P, Kennedy D (2004) The obesity epidemic. Science 304:1413CrossRefPubMedGoogle Scholar
  2. Barker DJ (1990) The fetal and infant origins of adult disease. BMJ 301:1111CrossRefPubMedGoogle Scholar
  3. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet 2:577–580CrossRefPubMedGoogle Scholar
  4. Barker DJ, Bull AR, Osmond C, Simmonds SJ (1990) Fetal and placental size and risk of hypertension in adult life. BMJ 301:259–262CrossRefPubMedGoogle Scholar
  5. Bassols J, Prats-Puig A, Vazquez-Ruiz M, Garcia-Gonzalez MM, Martinez-Pascual M, Avelli P, Martinez-Martinez R, Fabrega R, Colomer-Virosta C, Soriano-Rodriguez P, Diaz M, de Zegher F, Ibanez L, Lopez-Bermejo A (2010) Placental FTO expression relates to fetal growth. Int J Obes (Lond)Google Scholar
  6. Berenson GS (1980) Cardiovascular risk factors in children. Oxford University Press, New YorkGoogle Scholar
  7. Berenson GS (2005) Obesity—a critical issue in preventive cardiology: the Bogalusa Heart Study. Prev Cardiol 8:234–241 (quiz 242–243)CrossRefPubMedGoogle Scholar
  8. Berenson GS, Pickoff AS (1995) Preventive cardiology and its potential influence on the early natural history of adult heart diseases: the Bogalusa Heart Study and the Heart Smart Program. Am J Med Sci 310(Suppl 1):S133–S138PubMedGoogle Scholar
  9. Boissel S, Reish O, Proulx K, Kawagoe-Takaki H, Sedgwick B, Yeo GS, Meyre D, Golzio C, Molinari F, Kadhom N, Etchevers HC, Saudek V, Farooqi IS, Froguel P, Lindahl T, O’Rahilly S, Munnich A, Colleaux L (2009) Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 85:106–111CrossRefPubMedGoogle Scholar
  10. Broyles S, Katzmarzyk PT, Srinivasan SR, Chen W, Bouchard C, Freedman DS, Berenson GS (2010) The pediatric obesity epidemic continues unabated in Bogalusa, Louisiana. Pediatrics 125:900–905CrossRefPubMedGoogle Scholar
  11. Fabsitz RR, Carmelli D, Hewitt JK (1992) Evidence for independent genetic influences on obesity in middle age. Int J Obes Relat Metab Disord 16:657–666PubMedGoogle Scholar
  12. Farooqi IS, O’Rahilly S (2005) Monogenic obesity in humans. Annu Rev Med 56:443–458CrossRefPubMedGoogle Scholar
  13. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JR, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJ, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CN, Doney AS, Morris AD, Smith GD, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894CrossRefPubMedGoogle Scholar
  14. Godfrey KM, Barker DJ (2000) Fetal nutrition and adult disease. Am J Clin Nutr 71:1344S–1352SPubMedGoogle Scholar
  15. Hakanen M, Raitakari OT, Lehtimaki T, Peltonen N, Pahkala K, Sillanmaki L, Lagstrom H, Viikari J, Simell O, Ronnemaa T (2009) FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. J Clin Endocrinol Metab 94:1281–1287CrossRefPubMedGoogle Scholar
  16. Horikoshi M, Hara K, Ito C, Shojima N, Nagai R, Ueki K, Froguel P, Kadowaki T (2007) Variations in the HHEX gene are associated with increased risk of type 2 diabetes in the Japanese population. Diabetologia 50:2461–2466CrossRefPubMedGoogle Scholar
  17. Hsu FC, Lenchik L, Nicklas BJ, Lohman K, Register TC, Mychaleckyj J, Langefeld CD, Freedman BI, Bowden DW, Carr JJ (2005) Heritability of body composition measured by DXA in the diabetes heart study. Obes Res 13:312–319CrossRefPubMedGoogle Scholar
  18. Johnston LB, Clark AJ, Savage MO (2002) Genetic factors contributing to birth weight. Arch Dis Child Fetal Neonatal Ed 86:F2–F3CrossRefPubMedGoogle Scholar
  19. Jorgenson E, Witte JS (2006) Coverage and power in genomewide association studies. Am J Hum Genet 78:884–888CrossRefPubMedGoogle Scholar
  20. Li H, Wu Y, Loos RJ, Hu FB, Liu Y, Wang J, Yu Z, Lin X (2008) Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes 57:264–268CrossRefPubMedGoogle Scholar
  21. Luan J, Kerner B, Zhao JH, Loos RJ, Sharp SJ, Muthen BO, Wareham NJ (2009) A multilevel linear mixed model of the association between candidate genes and weight and body mass index using the Framingham longitudinal family data. BMC Proc 3(Suppl 7):S115CrossRefPubMedGoogle Scholar
  22. Magnus P (1984) Causes of variation in birth weight: a study of offspring of twins. Clin Genet 25:15–24CrossRefPubMedGoogle Scholar
  23. Morton NE (1955) The inheritance of human birth weight. Ann Hum Genet 20:125–134CrossRefPubMedGoogle Scholar
  24. Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM (2006) Prevalence of overweight and obesity in the United States, 1999–2004. JAMA 295:1549–1555CrossRefPubMedGoogle Scholar
  25. Olszewski PK, Fredriksson R, Olszewska AM, Stephansson O, Alsio J, Radomska KJ, Levine AS, Schioth HB (2009) Hypothalamic FTO is associated with the regulation of energy intake not feeding reward. BMC Neurosci 10:129CrossRefPubMedGoogle Scholar
  26. Parsons TJ, Power C, Manor O (2001) Fetal and early life growth and body mass index from birth to early adulthood in 1958 British cohort: longitudinal study. BMJ 323:1331–1335CrossRefPubMedGoogle Scholar
  27. Peeters A, Beckers S, Verrijken A, Roevens P, Peeters P, Van Gaal L, Van Hul W (2008) Variants in the FTO gene are associated with common obesity in the Belgian population. Mol Genet Metab 93:481–484CrossRefPubMedGoogle Scholar
  28. Price RA, Li WD, Zhao H (2008) FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs. BMC Med Genet 9:4CrossRefPubMedGoogle Scholar
  29. Schousboe K, Willemsen G, Kyvik KO, Mortensen J, Boomsma DI, Cornes BK, Davis CJ, Fagnani C, Hjelmborg J, Kaprio J, De Lange M, Luciano M, Martin NG, Pedersen N, Pietilainen KH, Rissanen A, Saarni S, Sorensen TI, Van Baal GC, Harris JR (2003) Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries. Twin Res 6:409–421CrossRefPubMedGoogle Scholar
  30. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, Strait J, Najjar S, Nagaraja R, Orru M, Usala G, Dei M, Lai S, Maschio A, Busonero F, Mulas A, Ehret GB, Fink AA, Weder AB, Cooper RS, Galan P, Chakravarti A, Schlessinger D, Cao A, Lakatta E, Abecasis GR (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3:e115CrossRefPubMedGoogle Scholar
  31. Singhal A, Wells J, Cole TJ, Fewtrell M, Lucas A (2003) Programming of lean body mass: a link between birth weight, obesity, and cardiovascular disease? Am J Clin Nutr 77:726–730PubMedGoogle Scholar
  32. The International HapMap Consortium (2005) A haplotype map of the human genome. Nature 437:1299–1320CrossRefGoogle Scholar
  33. Webber LS, Wattigney WA, Srinivasan SR, Berenson GS (1995) Obesity studies in Bogalusa. Am J Med Sci 310(Suppl 1):S53–S61PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hao Mei
    • 1
  • Wei Chen
    • 2
  • Sathanur R. Srinivasan
    • 2
  • Fan Jiang
    • 3
  • Nicholas Schork
    • 4
  • Sarah Murray
    • 4
  • Erin Smith
    • 4
  • Joanne D. So
    • 5
  • Gerald S. Berenson
    • 6
    Email author
  1. 1.Department of EpidemiologyTulane UniversityNew OrleansUSA
  2. 2.Tulane Center for Cardiovascular HealthTulane UniversityNew OrleansUSA
  3. 3.Shanghai Children’s Medical CenterShanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Scripps Genomic Medicine and Scripps Translational Science InstituteSan DiegoUSA
  5. 5.Tulane UniversityNew OrleansUSA
  6. 6.Center for Cardiovascular HealthNew OrleansUSA

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