Genetics of pediatric obesity

Pediatrics

Volumn 130, Issue 1, 2012, Pages 123-133

  Manco, Melania ^a   Dallapiccola, Bruno ^a  

^a BAMBINO GESÙ CHILDREN S HOSPITAL   (Italy)

Author keywords

Childhood; Genome wide association study; Heritability; Metabolic programming; Obesity

Indexed keywords

LEPTIN;

BODY MASS; CHILDHOOD OBESITY; DNA METHYLATION; ENERGY EXPENDITURE; EPIGENETICS; FTO GENE; GENE; GENE EXPRESSION; GENE FREQUENCY; GENE FUNCTION; GENE LOCUS; GENE MUTATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOMICS; GENOTYPE; GENOTYPE ENVIRONMENT INTERACTION; HETEROZYGOSITY; HOMOZYGOSITY; HORMONE BLOOD LEVEL; HUMAN; LOW BIRTH WEIGHT; MR4C GENE; ONSET AGE; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; TMEM18 GENE;

CHILD; EPIGENOMICS; GENE-ENVIRONMENT INTERACTION; GENETIC MARKERS; GENOME-WIDE ASSOCIATION STUDY; HUMANS; OBESITY; POLYMORPHISM, GENETIC;

EID: 84863508910     PISSN: 00314005     EISSN: 10984275     Source Type: Journal    
DOI: 10.1542/peds.2011-2717     Document Type: Review

References (90)

1. Han JC, Lawlor DA, Kimm SY. Childhood obesity. Lancet. 2010;375(9727):1737-1748
2. Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. 1997;27(4):325-351 (Pubitemid 27415169)
3. Speliotes EK, Willer CJ, Berndt SI, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937-948
4. Stranger BE, Stahl EA, Raj T. Progress and promise of genome-wide association studies for human complex trait genetics. Genetics. 2011;187(2):367-383
5. Brune BC, Gerlach MK, Seewald MJ, Brune TG. Early postnatal BMI adaptation is regulated during a fixed time period and mainly depends on maternal BMI. Obesity (Silver Spring). 2010;18(4):798-802
6. Hochberg Z, Feil R, Constancia M, et al. Child health, developmental plasticity, and epigenetic programming. Endocr Rev. 2011;32(2):159-224
7. Salsberry PJ, Reagan PB. Effects of heritability, shared environment, and nonshared intrauterine conditions on child and adolescent BMI. Obesity (Silver Spring). 2010;18(9):1775-1780
8. Haberstick BC, Lessem JM, McQueen MB, et al. Stable genes and changing environments: body mass index across adolescence and young adulthood. Behav Genet. 2010;40(4):495-504
9. Schousboe K, Willemsen G, Kyvik KO, et al. Sex differences in heritability of BMI: a comparative study of results from twin studies in eight countries. Twin Res. 2003;6(5):409-421 (Pubitemid 38019779)
10. Lajunen HR, Kaprio J, Keski-Rahkonen A, et al. Genetic and environmental effects on body mass index during adolescence: a prospective study among Finnish twins. Int J Obes (Lond). 2009;33(5):559-567
11. Loos RJ. Genetics: genome-wide risk profiles - will they change your life(style)? Nat Rev Endocrinol. 2011;7(5):252-254
12. Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. 2009;461(7265):747-753
13. Marian AJ, Belmont J. Strategic approaches to unraveling genetic causes of cardiovascular diseases. Circ Res. 2011;108(10):1252-1269.
14. Willer CJ, Speliotes EK, Loos RJ, et al Wellcome Trust Case Control Consortium; Genetic Investigation of ANthropometric Traits Consortium. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2009;41(1):25-34
15. den Hoed M, Ekelund U, Brage S, et al. Genetic susceptibility to obesity and related traits in childhood and adolescence: influence of loci identified by genome-wide association studies. Diabetes. 2010;59(11):2980-2988
16. Frayling TM, Timpson NJ, Weedon MN, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science. 2007;316(5826):889-894 (Pubitemid 46764279)
17. Dina C, Meyre D, Gallina S, et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nat Genet. 2007;39(6):724-726 (Pubitemid 46848595)
18. Jess T, Zimmermann E, Kring SI, et al. Impact on weight dynamics and general growth of the common FTO rs9939609: a longitudinal Danish cohort study. Int J Obes (Lond). 2008;32(9):1388-1394
19. Haworth CM, Carnell S, Meaburn EL, Davis OS, Plomin R, Wardle J. Increasing heritability of BMI and stronger associations with the FTO gene over childhood. Obesity (Silver Spring). 2008;16(12):2663-2668
20. Kring SI, Holst C, Zimmermann E, et al. FTO gene associated fatness in relation to body fat distribution and metabolic traits throughout a broad range of fatness. PLoS ONE. 2008;3(8):e2958
21. Cecil JE, Tavendale R, Watt P, Hetherington MM, Palmer CN. An obesity-associated FTO gene variant and increased energy intake in children. N Engl J Med. 2008;359(24):2558-2566
22. Wardle J, Llewellyn C, Sanderson S, Plomin R. The FTO gene and measured food intake in children. Int J Obes (Lond). 2009;33(1):42-45
23. Wardle J, Carnell S, Haworth CM, Farooqi IS, O'Rahilly S, Plomin R. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab. 2008;93(9):3640-3643
24. Rzehak P, Scherag A, Grallert H, et al GINI and LISA Study Group. Associations between BMI and the FTO gene are age dependent: results from the GINI and LISA birth cohort studies up to age 6 years. Obes Facts. 2010;3(3):173-180
25. Scuteri A, Sanna S, Chen WM, et al. Genomewide association scan shows genetic variants in the FTO gene are associated with obesityrelated traits. PLoS Genet. 2007;3(7):e115
26. Ohashi J, Naka I, Kimura R, et al. FTO polymorphisms in oceanic populations. J Hum Genet. 2007;52(12):1031-1035 (Pubitemid 350164612)
27. Grant SF, Li M, Bradfield JP, et al. Association analysis of the FTO gene with obesity in children of Caucasian and African ancestry reveals a common tagging SNP. PLoS One. 2008;3(3):e1746
28. Li H, Wu Y, Loos RJ, et al. Variants in the fat mass- and obesity-associated (FTO) gene are not associated with obesity in a Chinese Han population. Diabetes. 2008;57(1):264-268
29. Kaakinen M, Läärä E, Pouta A, et al. Life-course analysis of a fat mass and obesity-associated (FTO) gene variant and body mass index in the Northern Finland Birth Cohort 1966 using structural equation modeling. Am J Epidemiol. 2010;172(6):653-665
30. Labayen I, Ruiz JR, Ortega FB, et al. Association between the FTO rs9939609 polymorphism and leptin in European adolescents: a possible link with energy balance control. The HELENA study. Int J Obes. 2011;35(1):66-71
31. Scott RA, Bailey ME, Moran CN, et al. FTO genotype and adiposity in children: physical activity levels influence the effect of the risk genotype in adolescent males. Eur J Hum Genet. 2010;18(12):1339-1343
32. Hinney A, Nguyen TT, Scherag A, et al. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS ONE. 2007;2(12):e1361
33. Hunt SC, Stone S, Xin Y, et al. Association of the FTO gene with BMI. Obesity (Silver Spring). 2008;16(4):902-904 (Pubitemid 351465652)
34. López-Bermejo A, Petry CJ, Díaz M, et al. The association between the FTO gene and fat mass in humans develops by the postnatal age of two weeks. J Clin Endocrinol Metab. 2008;93(4):1501-1505 (Pubitemid 351519755)
35. Hakanen M, Raitakari OT, Lehtimäki T, et al. 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. 2009;94(4):1281-1287
36. Rutters F, Nieuwenhuizen AG, Bouwman F, Mariman E, Westerterp-Plantenga MS. Associations between a single nucleotide polymorphism of the FTO Gene (rs9939609) and obesity-related characteristics over time during puberty in a Dutch children cohort. J Clin Endocrinol Metab. 2011;96(6):E939-E942
37. Hebebrand J. Putting the greater dimensions of obesity into perspective. Obes Facts. 2010;3(6):341-342
38. Hardy R, Wills AK, Wong A, et al. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum Mol Genet. 2010;19(3):545-552
39. Krude H, Biebermann H, Gruters A. Mutations in the human proopiomelanocortin gene. Ann N Y Acad Sci. 2003;994:233-239 (Pubitemid 36793872)
40. Lubrano-Berthelier C, Dubern B, Lacorte JM, et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab. 2006;91(5):1811-1818
41. Loos RJ, Lindgren CM, Li S, et al; Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial; KORA; Nurses' Health Study; Diabetes Genetics Initiative; SardiNIA Study Wellcome Trust Case Control Consortium; FUSION. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet. 2008;40(6):768-775
42. Grant SF, Bradfield JP, Zhang H, et al. Investigation of the locus near MC4R with childhood obesity in Americans of European and African ancestry. Obesity (Silver Spring). 2009;17(7):1461-1465
43. Tao YX. Molecular mechanisms of the neural melanocortin receptor dysfunction in severe early onset obesity. Mol Cell Endocrinol. 2005;239(1-2):1-14
44. Vaisse C, Clément K, Durand E, Hercberg S, Guy-Grand B, Froguel P. Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest. 2000;106(2):253-262 (Pubitemid 30483129)
45. Dempfle A, Hinney A, Heinzel-Gutenbrunner M, et al. Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index. J Med Genet. 2004;41 (10):795-800 (Pubitemid 39389299)
46. Farooqi IS, Keogh JM, Yeo GSH, Lank EJ, Cheetham T, O'Rahilly S. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095 (Pubitemid 36337319)
47. Martinelli CE, Keogh JM, Greenfield JR, et al. Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion. J Clin Endocrinol Metab. 2011;96(1):E181-E188
48. Loos RJ. The genetic epidemiology of melanocortin 4 receptor variants. Eur J Pharmacol. 2011;660(1):156-164
49. Elks CE, Loos RJ, Sharp SJ, et al. Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med. 2010;7(5):e1000284
50. Petry CJ, López-Bermejo A, Díaz M, et al. Association between a common variant near MC4R and change in body mass index develops by two weeks of age. Horm Res Paediatr. 2010;73(4):275-280
51. Almén MS, Jacobsson JA, Shaik JH, et al. The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Med Genet. 2010;11:58
52. Zhao J, Bradfield JP, Li M, et al. The role of obesity-associated loci identified in genomewide association studies in the determination of pediatric BMI. Obesity (Silver Spring). 2009;17(12):2254-2257
53. Scherag A, Dina C, Hinney A, et al. Two new Loci for body-weight regulation identified in a joint analysis of genome-wide association studies for early-onset extreme obesity in French and German study groups. PLoS Genet. 2010;6(4):e1000916
54. Ruiz JR, Labayen I, Ortega FB, et al HELENA Study Group. Attenuation of the effect of the FTO rs9939609 polymorphism on total and central body fat by physical activity in adolescents: the HELENA study. Arch Pediatr Adolesc Med. 2010;164(4):328-333
55. Cauchi S, Stutzmann F, Cavalcanti-Proença C, et al. Combined effects of MC4R and FTO common genetic variants on obesity in European general populations. J Mol Med (Berl). 2009;87(5):537-546
56. Vimaleswaran KS, Franks PW, Brage S, et al. Lack of association between PCK1 polymorphisms and obesity, physical activity, and fitness in European Youth Heart Study (EYHS). Obesity (Silver Spring). 2010;18(10):1975-1980
57. Liu G, Zhu H, Lagou V, et al. FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in Europeanand African-American youth. BMC Med Genet. 2010;11:57
58. Kilpeläinen TO, Qi L, Brage S, et al. Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children. PLoS Med. 2011;8(11):e1001116
59. Scherag A, Kleber M, Boes T, et al. SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents. Obesity (Silver Spring). 2011;20(2):466-470
60. Xi B, Shen Y, Zhang M, et al. The common rs9939609 variant of the fat mass and obesity-associated gene is associated with obesity risk in children and adolescents of Beijing, China. BMC Med Genet. 2010;11:107
61. Troiano RP, Berrigan D, Dodd KW, Mâsse LC, Tilert T, McDowell M. Physical activity in the United States measured by accelerometer. Med Sci Sports Exerc. 2008;40(1):181-188
62. Johnson L, van Jaarsveld CH, Emmett PM, et al. Dietary energy density affects fat mass in early adolescence and is not modified by FTO variants. PLoS ONE. 2009;4(3):e4594
63. Lagou V, Scott RA, Manios Y, et al. Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study. Obesity (Silver Spring). 2008;16(4):913-918 (Pubitemid 351465655)
64. Dedoussis GV, Manios Y, Kourlaba G, et al. An age-dependent diet-modified effect of the PPARg Pro12Ala polymorphism in children. Metabolism. 2011;60(4):467-473
65. Blaxter M. Genetics. Revealing the dark matter of the genome. Science. 2010;330(6012):1758-1759
66. Lillycrop KA, Burdge GC. Epigenetic changes in early life and future risk of obesity. Int J Obes (Lond). 2011;35(1):72-83
67. Wolff GL, Kodell RL, Moore SR, Cooney CA. Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/ a mice. FASEB J. 1998;12(11):949-957 (Pubitemid 28359576)
68. Feil R. Environmental and nutritional effects on the epigenetic regulation of genes. Mutat Res. 2006;600(1-2):46-57
69. Gallou-Kabani C, Vigé A, Gross MS, et al. Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods. Am J Physiol Endocrinol Metab. 2007;292(4):E1095-E1100 (Pubitemid 46536509)
70. Howie GJ, Sloboda DM, Kamal T, Vickers MH. Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009;587(pt 4):905-915
71. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727):1466-1469 (Pubitemid 40791300)
72. Fowden AL, Ward JW, Wooding FP, Forhead AJ, Constancia M. Programming placental nutrient transport capacity. J Physiol. 2006; 572(pt 1):5-15
73. Gluckman PD, Hanson MA, Cooper C, Thornburg KL. Effect of in utero and earlylife conditions on adult health and disease. N Engl J Med. 2008;359(1):61-73
74. Filiberto AC, Maccani MA, Koestler D, et al. Birthweight is associated with DNA promoter methylation of the glucocorticoid receptor in human placenta. Epigenetics. 2011;6(5):566-572
75. Godfrey KM, Sheppard A, Gluckman PD, et al. Epigenetic gene promoter methylation at birth is associated with child's later adiposity. Diabetes. 2011;60(5):1528-1534
76. Heijmans BT, Tobi EW, Stein AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008;105(44):17046-17049
77. Barker DJ. The fetal and infant origins of adult disease. BMJ. 1990;301(6761):1111 (Pubitemid 20387183)
78. Wang X, Zuckerman B, Coffman GA, Corwin MJ. Familial aggregation of low birth weight among whites and blacks in the United States. N Engl J Med. 1995;333(26):1744-1749 (Pubitemid 26007127)
79. Magnus P, Bakketeig LS, Hoffman H. Birth weight of relatives by maternal tendency to repeat small-for-gestational-age (SGA) births in successive pregnancies. Acta Obstet Gynecol Scand Suppl. 1997;165:35-38
80. Morgan AR, Thompson JM, Murphy R, et al. Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study. BMC Med Genet. 2010;11:125
81. Chung WK, Leibel RL. Considerations regarding the genetics of obesity. Obesity (Silver Spring). 2008;16(suppl 3):S33-S39
82. Freathy RM, Mook-Kanamori DO, Sovio U, et al. Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight. Nat Genet. 2010;42(5):430-435
83. Kilpeläinen TO, den Hoed M, Ong KK, et al Early Growth Genetics Consortium. Obesitysusceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals. Am J Clin Nutr. 2011;93(4):851-860
84. Silventoinen K, Kaprio J. Genetics of tracking of body mass index from birth to late middle age: evidence from twin and family studies. Obes Facts. 2009;2(3):196-202
85. Wardle J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr. 2008;87(2):398-404 (Pubitemid 351226077)
86. Hopper JL, Bishop DT, Easton DF. Populationbased family studies in genetic epidemiology. Lancet. 2005;366(9494):1397-1406 (Pubitemid 41443407)
87. Silventoinen K, Rokholm B, Kaprio J, Sørensen TI. The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes (Lond). 2010;34(1):29-40
88. Plomin R. Commentary: Why are children in the same family so different? Non-shared environment three decades later. Int J Epidemiol. 2011;40(3):582-592
89. Exposome and exposomics. Atlanta, GA: Centers for Disease Control and Prevention. Available at: www.cdc.gov/niosh/topics/exposome/ Accessed September 6, 2011
90. NCBI RefSeq. NCBI Reference Sequences. Bethesda, MD: National Center for Biotechnology Information. Available at: www.ncbi.nlm.nih.gov/RefSeq/ Accessed December 15, 2011