The Genetics of Pediatric Obesity

Trends in Endocrinology and Metabolism

Volumn 26, Issue 12, 2015, Pages 711-721

  Chesi, Alessandra ^a   Grant, Struan F A ^a,b  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; CHILD; CHILDHOOD OBESITY; ENVIRONMENTAL FACTOR; FAMILY STUDY; GENE LOCUS; GENETIC ASSOCIATION; HEREDITY; HUMAN; HUMAN GENETICS; META ANALYSIS (TOPIC); NONHUMAN; PRIORITY JOURNAL; REVIEW; GENETIC PREDISPOSITION; GENETICS; SINGLE NUCLEOTIDE POLYMORPHISM;

CHILD; GENETIC LOCI; GENETIC PREDISPOSITION TO DISEASE; HUMANS; PEDIATRIC OBESITY; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84949624773     PISSN: 10432760     EISSN: 18793061     Source Type: Journal    
DOI: 10.1016/j.tem.2015.08.008     Document Type: Review

References (100)

1. World Health Organization Obesity and Overweight. Fact Sheet 311 2012, WHO.
2. Eckel R.H. Obesity: a disease or a physiologic adaptation for survival?. Obesity Mechanisms and Clinical Management 2003, 3-30. Lippincot, Williams & Wilkins. R.H. Eckel (Ed.).
3. Ogden C.L., et al. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA 2014, 311:806-814.
4. Daniels S.R., et al. Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation 2005, 111:1999-2012.
5. Freedman D.S., et al. The relation of childhood BMI to adult adiposity: the Bogalusa Heart Study. Pediatrics 2005, 115:22-27.
6. Barlow S.E., the Expert Committee Expert Committee recommendations regarding the prevention, assessment, and treatment of child and adolescent overweight and obesity: summary report. Pediatrics 2007, 120(Suppl. 4):S164-S192.
7. Stergiakouli E., et al. Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3. Obesity 2014, 22:2252-2259.
8. Bennett W.E., et al. The natural history of weight percentile changes in the first year of life. JAMA Pediatr. 2014, 168:681-682.
9. Johnson W., et al. Characterization of the infant BMI peak: sex differences, birth year cohort effects, association with concurrent adiposity, and heritability. Am. J. Hum. Biol. 2013, 25:378-388.
10. Wen X., et al. Childhood body mass index trajectories: modeling, characterizing, pairwise correlations and socio-demographic predictors of trajectory characteristics. BMC Med. Res. Methodol. 2012, 12:38.
11. Roy S.M., et al. Body mass ondex (BMI) trajectories in infancy differ by population ancestry and may presage disparities in early childhood obesity. J. Clin. Endocrinol. Metab. 2015, 100:1551-1560.
12. Silverwood R.J., et al. BMI peak in infancy as a predictor for later BMI in the Uppsala Family Study. Int. J. Obes. 2009, 33:929-937.
13. Sovio U., et al. How do changes in body mass index in infancy and childhood associate with cardiometabolic profile in adulthood? Findings from the Northern Finland Birth Cohort 1966 Study. Int. J. Obes. 2014, 38:53-59.
14. Min J., et al. Variation in the heritability of body mass index based on diverse twin studies: a systematic review. Obes. Rev. 2013, 14:871-882.
15. Stunkard A.J., et al. An adoption study of human obesity. N. Engl. J. Med. 1986, 314:193-198.
16. Sorensen T.I., et al. Genetics of obesity in adult adoptees and their biological siblings. BMJ 1989, 298:87-90.
17. Knowler W.C., et al. Diabetes mellitus in the Pima Indians: incidence, risk factors and pathogenesis. Diab. Metab. Rev. 1990, 6:1-27.
18. Kondo I., et al. Exclusion mapping of the Cohen syndrome gene from the Prader-Willi syndrome locus. Clin. Genet. 1990, 38:422-426.
19. Russell-Eggitt I.M., et al. Alstrom syndrome. Report of 22 cases and literature review. Ophthalmology 1998, 105:1274-1280.
20. Forsythe E., Beales P.L. Bardet-Biedl syndrome. Eur. J. Hum. Genet. 2013, 21:8-13.
21. Zhang Y., et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994, 372:425-432.
22. Chua S.C., et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996, 271:994-996.
23. Farooqi I.S., O'Rahilly S. 20 years of leptin: human disorders of leptin action. J. Endocrinol. 2014, 223:T63-T70.
24. + exchanger NHE2. Am. J. Physiol. 1999, 277:G383-G390.
25. Yeo G.S., et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat. Neurosci. 2004, 7:1187-1189.
26. Holder J.L., et al. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Mol. Genet. 2000, 9:101-108.
27. Yeo G.S., et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat. Genet. 1998, 20:111-112.
28. Farooqi I.S., et al. Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J. Clin. Invest. 2000, 106:271-279.
29. McCarthy M.I., et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat. Rev. Genet. 2008, 9:356-369.
30. Herbert A., et al. A common genetic variant is associated with adult and childhood obesity. Science 2006, 312:279-283.
31. Loos R.J., et al. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007, 315:187.
32. Dina C., et al. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007, 315:187.
33. Rosskopf D., et al. Comment on 'A common genetic variant is associated with adult and childhood obesity'. Science 2007, 315:187.
34. Lyon H.N., et al. The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts. PLoS Genet. 2007, 3:e61.
35. Hotta K., et al. INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese. J. Hum. Genet. 2008, 53:857-862.
36. Frayling T.M., et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007, 316:889-894.
37. Fawcett K.A., Barroso I. The genetics of obesity: FTO leads the way. Trends Genet. 2010, 26:266-274.
38. Grant S.F., 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:e1746.
39. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 2007, 447:661-678. Wellcome Trust Case Control Consortium.
40. Zeggini E., et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 2007, 316:1336-1341.
41. Loos R.J., et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat. Genet. 2008, 40:768-775.
42. Willer C.J., et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat. Genet. 2009, 41:25-34.
43. Speliotes E.K., et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat. Genet. 2010, 42:937-948.
44. Thorleifsson G., et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat. Genet. 2009, 41:18-24.
45. Monda K.L., et al. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat. Genet. 2013, 45:690-696.
46. Wen W., et al. Meta-analysis identifies common variants associated with body mass index in east Asians. Nat. Genet. 2012, 44:307-311.
47. Wen W., et al. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Hum. Mol. Genet. 2014, 23:5492-5504.
48. Locke A.E., et al. Genetic studies of body mass index yield new insights for obesity biology. Nature 2015, 518:197-206.
49. Berndt S.I., et al. Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nat. Genet. 2013, 45:501-512.
50. Liu C.T., et al. Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS Genet. 2013, 9:e1003681.
51. Shungin D., et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature 2015, 518:187-196.
52. Heid I.M., et al. Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat. Genet. 2010, 42:949-960.
53. Barker D.J. Sir Richard Doll Lecture. Developmental origins of chronic disease. Public Health 2012, 126:185-189.
54. Gluckman P.D., et al. Effect of in utero and early-life conditions on adult health and disease. N. Engl. J. Med. 2008, 359:61-73.
55. Zhao J., et al. Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity 2011, 19:2436-2439.
56. Zhao J., et al. The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI. Obesity 2009, 17:2254-2257.
57. den Hoed M., et al. Genetic susceptibility to obesity and related traits in childhood and adolescence: influence of loci identified by genome-wide association studies. Diabetes 2010, 59:2980-2988.
58. Hardy R., et al. Life course variations in the associations between FTO and MC4R gene variants and body size. Hum. Mol. Genet. 2010, 19:545-552.
59. Elks C.E., et al. Genetic markers of adult obesity risk are associated with greater early infancy weight gain and growth. PLoS Med. 2010, 7:e1000284.
60. Belsky D.W., et al. Polygenic risk, rapid childhood growth, and the development of obesity: evidence from a 4-decade longitudinal study. Arch. Pediatr. Adolesc. Med. 2012, 166:515-521.
61. Warrington N.M., et al. Association of a body mass index genetic risk score with growth throughout childhood and adolescence. PLoS ONE 2013, 8:e79547.
62. Vogelezang S., et al. Adult adiposity susceptibility loci, early growth and general and abdominal fatness in childhood: the Generation R Study. Int. J. Obes. 2015, 39:1001-1009.
63. Zhao J., et al. Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI. Diabetes 2010, 59:751-755.
64. Zhao J., et al. BMD-associated variation at the Osterix locus is correlated with childhood obesity in females. Obesity 2011, 19:1311-1314.
65. Lopez-Bermejo A., 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, 93:1501-1505.
66. Marsh J.A., et al. Fat mass and obesity-associated obesity-risk genotype is associated with lower foetal growth: an effect that is reversed in the offspring of smoking mothers. J. Dev. Orig. Health Dis. 2012, 3:10-20.
67. Sovio U., et al. 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 Genet. 2011, 7:e1001307.
68. Rolland-Cachera M.F., et al. Early adiposity rebound: causes and consequences for obesity in children and adults. Int. J. Obes. 2006, 30(Suppl 4):S11-S17.
69. Barker D.J., et al. Trajectories of growth among children who have coronary events as adults. N. Engl. J. Med. 2005, 353:1802-1809.
70. Gerken T., et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007, 318:1469-1472.
71. Lein E.S., et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 2007, 445:168-176.
72. Cecil J.E., et al. An obesity-associated FTO gene variant and increased energy intake in children. N. Engl. J. Med. 2008, 359:2558-2566.
73. Church C., et al. Overexpression of Fto leads to increased food intake and results in obesity. Nat. Genet. 2010, 42:1086-1092.
74. Fischer J., et al. Inactivation of the Fto gene protects from obesity. Nature 2009, 458:894-898.
75. Smemo S., et al. Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 2014, 507:371-375.
76. Stratigopoulos G., et al. Regulation of Fto/Ftm gene expression in mice and humans. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2008, 294:R1185-R1196.
77. Stratigopoulos G., et al. Cut-like homeobox 1 (CUX1) regulates expression of the fat mass and obesity-associated and retinitis pigmentosa GTPase regulator-interacting protein-1-like (RPGRIP1L) genes and coordinates leptin receptor signaling. J. Biol. Chem. 2011, 286:2155-2170.
78. Meyre D., et al. Prevalence of loss-of-function FTO mutations in lean and obese individuals. Diabetes 2010, 59:311-318.
79. Scherag 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:e1000916.
80. Bradfield J.P., et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat. Genet. 2012, 44:526-531.
81. Wheeler E., et al. Genome-wide SNP and CNV analysis identifies common and low-frequency variants associated with severe early-onset obesity. Nat. Genet. 2013, 45:513-517.
82. Warrington N.M., et al. A genome-wide association study of body mass index across early life and childhood. Int. J. Epidemiol. 2015, 44:700-712.
83. Grant S.F., et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat. Genet. 2006, 38:320-323.
84. Helgason A., et al. Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution. Nat. Genet. 2007, 39:218-225.
85. Scuteri A., et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet. 2007, 3:e115.
86. Adeyemo A., et al. FTO genetic variation and association with obesity in West Africans and African Americans. Diabetes 2010, 59:1549-1554.
87. Hassanein M.T., et al. Fine mapping of the association with obesity at the FTO locus in African-derived populations. Hum. Mol. Genet. 2010, 19:2907-2916.
88. Blakemore A.I., et al. A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. Obesity 2009, 17:1549-1553.
89. Bochukova E.G., et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 2010, 463:666-670.
90. Walters R.G., et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 2010, 463:671-675.
91. Jacquemont S., et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 2011, 478:97-102.
92. Glessner J.T., et al. A genome-wide study reveals copy number variants exclusive to childhood obesity cases. Am. J. Hum. Genet. 2010, 87:661-666.
93. Jarick I., et al. Novel common copy number variation for early onset extreme obesity on chromosome 11q11 identified by a genome-wide analysis. Hum. Mol. Genet. 2011, 20:840-852.
94. Slatkin M. Epigenetic inheritance and the missing heritability problem. Genetics 2009, 182:845-850.
95. Cortijo S., et al. Mapping the epigenetic basis of complex traits. Science 2014, 343:1145-1148.
96. Leff S.E., et al. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nat. Genet. 1992, 2:259-264.
97. Nicholls R.D., et al. Imprinting in Prader-Willi and Angelman syndromes. Trends Genet. 1998, 14:194-200.
98. Dong C., et al. Possible genomic imprinting of three human obesity-related genetic loci. Am. J. Hum. Genet. 2005, 76:427-437.
99. Zuk O., et al. The mystery of missing heritability: genetic interactions create phantom heritability. Proc. Natl. Acad. Sci. U.S.A. 2012, 109:1193-1198.
100. Haberstick B.C., et al. Stable genes and changing environments: body mass index across adolescence and young adulthood. Behav. Genet. 2010, 40:495-504.