Genes and the Predisposition to Obesity

Handbook of Obesity: Epidemiology, Etiology, and Physiopathology: Volume 1, Third Edition

Volumn 1, Issue , 2014, Pages 105-119

  den Hoed, Marcel ^a,b   Loos, Ruth J F ^a,c  

^a MRC EPIDEMIOLOGY UNIT   (United Kingdom)

^b UPPSALA UNIVERSITY   (Sweden)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85054234159     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1201/b16473-14     Document Type: Chapter

References (121)

1. Flegal KM, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in the distribution of body mass index among US adults, 1999-2010. JAMA 2012;307:491-7.
2. Ogden CL, Carroll MD, Kit BK, et al. Prevalence of obesity and trends in body mass index among US children and adoles-cents, 1999-2010. JAMA 2012;307:483-90.
3. Cunningham SA, Ruben JD, Venkat Narayan KM. Health of foreign-born people in the United States: A review. Health Place 2008;14:623-35.
4. Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: Shaped by global drivers and local environments. Lancet 2011;378:804-14.
5. Elks CE, den Hoed M, Zhao JH, et al. Variability in the heritability of body masss index: A systematic review and meta-regression. Front Endocrinol. 2012;3:29.
6. Saunders CL, Chiodini BD, Sham P, et al. Meta-analysis of genome-wide linkage studies in BMI and obesity. Obesity (Silver Spring) 2007;15:2263-75.
7. Fan W, Boston BA, Kesterson RA, et al. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature 1997;385:165-8.
8. Flier JS, Harris M, Hollenberg AN. Leptin, nutrition, and the thyroid: The why, the wherefore, and the wiring. J Clin Invest 2000;105:859-61.
9. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997;88:131-41.
10. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med 2003;348:1085-95.
11. Wang D, Ma J, Zhang S, et al. Association of the MC4R V103I polymorphism with obesity: A Chinese case-control study and meta-analysis in 55,195 individuals. Obesity 2010;18:573-9.
12. Stutzmann F, Vatin V, Cauchi S, et al. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obe-sity: The two facets of a Janus obesity gene. Hum Mol Genet 2007;16:1837-44.
13. Krief S, Lonnqvist F, Raimbault S, et al. Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest 1993;91:344-9.
14. Lonnqvist F, Thome A, Nilsell K, et al. A pathogenic role of visceral fat beta 3-adrenoceptors in obesity. J Clin Invest 1995;95:1109-16.
15. Kurokawa N, Young EH, Oka Y, et al. The ADRB3 Trp64Arg variant and BMI: A meta-analysis of 44 833 individuals. Int J Obes (Lond) 2008;32:1240-9.
16. Okada Y, Kubo M, Ohmiya H, et al. Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. Nat Genet 2012;44:302-6.
17. Wen W, Cho YS, Zheng W, et al. Meta-analysis identifies common variants associated with body mass index in east Asians. Nat Genet 2012;44:307-11.
18. Seidah NG, Benjannet S, Hamelin J, et al. The subtilisin/kexin family of precursor convertases. Emphasis on PC1, PC2/7B2, POMC and the novel enzyme SKI-1. Ann N Y Acad Sci 1999; 885:57-74.
19. Farooqi IS, Volders K, Stanhope R, et al. Hyperphagia and early-onset obesity due to a novel homozygous missense muta-tion in prohormone convertase 1/3. J Clin Endocrinol Metab 2007;92:3369-73.
20. Jackson RS, Creemers JW, Farooqi IS, et al. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 2003; 112:1550-60.
21. Jackson RS, Creemers JW, Ohagi S, et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 1997;16:303-6.
22. Benzinou M, Creemers JW, Choquet H, et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nat Genet 2008;40:943-5.
23. Kilpelainen TO, Bingham SA, Khaw KT, et al. Association of variants in the PCSK1 gene with obesity in the EPIC-Norfolk study. Hum Mol Genet 2009;18:3496-501.
24. Fox EA, Byerly MS. A mechanism underlying mature-onset obesity: Evidence from the hyperphagic phenotype of brain-derived neurotrophic factor mutants. Am J Physiol Regul Integr Comp Physiol 2004;286:R994-1004.
25. Kernie SG, Liebl DJ, Parada LF. BDNF regulates eating behavior and locomotor activity in mice. EMBO J 2000;19:1290-300.
26. Rios M, Fan G, Fekete C, et al. Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obe-sity and hyperactivity. Mol Endocrinol 2001;15:1748-57.
27. Chen ZY, Patel PD, Sant G, et al. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular traf-ficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 2004; 24:4401-11.
28. Shugart YY, Chen L, Day IN, et al. Two British women studies replicated the association between the Val66Met polymor-phism in the brain-derived neurotrophic factor (BDNF) and BMI. Eur J Hum Genet 2009;17:1050-5.
29. Hong KW, Lim JE, Go MJ, et al. Recapitulation of the association of the Val66Met polymorphism of BDNF gene with BMI in Koreans. Obesity (Silver Spring) 2012;20:1871-5.
30. 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;42:937-48.
31. Enattah NS, Sahi T, Savilahti E, et al. Identification of a variant associated with adult-type hypolactasia. Nat Genet 2002; 30:233-7.
32. Bersaglieri T, Sabeti PC, Patterson N, et al. Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet 2004;74:1111-20.
33. Coelho M, Luiselli D, Bertorelle G, et al. Microsatellite variation and evolution of human lactase persistence. Hum Genet 2005; 117:329-39.
34. Lewinsky RH, Jensen TG, Moller J, et al. T-13910 DNA variant associated with lactase persistence interacts with Oct-1 and stimulates lactase promoter activity in vitro. Hum Mol Genet 2005;14:3945-53.
35. Kettunen J, Silander K, Saarela O, et al. European lactase persistence genotype shows evidence of association with increase in body mass index. Hum Mol Genet 2010;19:1129-36.
36. Brondel L, Romer MA, Nougues PM, et al. Acute partial sleep deprivation increases food intake in healthy men. Am J Clin Nutr 2010;91:1550-9.
37. Tasali E, Leproult R, Ehrmann DA, et al. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci USA 2008;105:1044-9.
38. Claustrat B, Brun J, Chazot G. The basic physiology and pathophysiology of melatonin. Sleep Med Rev 2005; 9:11-24.
39. Bouatia-Naji N, Bonnefond A, Cavalcanti-Proenca C, et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nat Genet 2009;41:89-94.
40. Prokopenko I, Langenberg C, Florez JC, et al. Variants in MTNR1B influence fasting glucose levels. Nat Genet 2009; 41:77-81.
41. Andersson EA, Holst B, Sparso T, et al. MTNR1B G24E variant associates with BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Diabetes 2010;59:1539-48.
42. Suganami T, Tanimoto-Koyama K, Nishida J, et al. Role of the toll-like receptor 4/NF-kappaB pathway in saturated fatty acid-induced inflammatory changes in the interaction between adipocytes and macrophages. Arterioscler Thromb Vasc Biol 2007;27:84-91.
43. Tsukumo DM, Carvalho-Filho MA, Carvalheira JB, et al. Loss-of-function mutation in toll-like receptor 4 prevents diet-induced obesity and insulin resistance. Diabetes 2007; 56:1986-98.
44. Reyna SM, Ghosh S, Tantiwong P, et al. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 2008;57:2595-602.
45. de Mello VD, Kolehmainen M, Pulkkinen L, et al. Downregulation of genes involved in NFkappaB activation in peripheral blood mononuclear cells after weight loss is associated with the improvement of insulin sensitivity in individuals with the metabolic syndrome: The GENOBIN study. Diabetologia 2008;51:2060-7.
46. Weyrich P, Staiger H, Stancakova A, et al. The D299G/T399I toll-like receptor 4 variant associates with body and liver fat: Results from the TULIP and METSIM Studies. PLoS One 2010;5:e13980.
47. Maddux BA, Sbraccia P, Kumakura S, et al. Membrane glycoprotein PC-1 and insulin resistance in non-insulin-dependent diabetes mellitus. Nature 1995;373:448-51.
48. McAteer JB, Prudente S, Bacci S, et al. The ENPP1 K121Q polymorphism is associated with type 2 diabetes in European populations: Evidence from an updated meta-analysis in 42,042 subjects. Diabetes 2008;57:1125-30.
49. Wang R, Zhou D, Xi B, et al. ENPP1/PC-1 gene K121Q polymorphism is associated with obesity in European adult populations: Evidence from a meta-analysis involving 24,324 subjects. Biomed Environ Sci 2011;24:200-6.
50. Hotta M, Kuriyama H, Arai K, et al. Fibroblast growth factor inhibits locomotor activity as well as feeding behavior of rats. Eur J Pharmacol 2001;416:101-6.
51. Sun HD, Malabunga M, Tonra JR, et al. Monoclonal antibody antagonists of hypothalamic FGFR1 cause potent but reversible hypophagia and weight loss in rodents and monkeys. Am J Physiol Endocrinol Metab 2007;292:E964-76.
52. Jiao H, Arner P, Dickson SL, et al. Genetic association and gene expression analysis identify FGFR1 as a new suscep-tibility gene for human obesity. J Clin Endocrinol Metab 2011;96:E962-6.
53. Farooqi IS, O’Rahilly S. Mutations in ligands and receptors of the leptin-melanocortin pathway that lead to obesity. Nat Clin Pract Endocrinol Metab 2008;4:569-77.
54. Chen H, Charlat O, Tartaglia LA, et al. Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 1996;84:491-5.
55. Mazen I, El-Gammal M, Abdel-Hamid M, et al. Homozygosity for a novel missense mutation in the leptin receptor gene (P316T) in two Egyptian cousins with severe early onset obesity. Mol Genet Metab 2011;102:461-4.
56. Bender N, Allemann N, Marek D, et al. Association between variants of the leptin receptor gene (LEPR) and overweight: A systematic review and an analysis of the CoLaus study. PLoS One 2011;6:e26157.
57. Sun Q, Cornelis MC, Kraft P, et al. Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels. Hum Mol Genet 2010;19:1846-55.
58. International Human Genome Sequencing Consortium. Finishing the euchromatic sequence of the human genome. Nature 2004; 431:931-45.
59. Frazer KA, Ballinger DG, Cox DR, et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007;449:851-61.
60. Sudmant PH, Kitzman JO, Antonacci F, et al. Diversity of human copy number variation and multicopy genes. Science 2010;330:641-6.
61. 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;316:889-94.
62. Scuteri A, Sanna S, Chen WM, et al. Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 2007;3:e115.
63. Loos RJ, Lindgren CM, Li S, et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 2008;40:768-75.
64. Chambers JC, Elliott P, Zabaneh D, et al. Common genetic variation near MC4R is associated with waist circumference and insulin resistance. Nat Genet 2008;40:716-8.
65. GIANT Consortium. Available from: http://www.broadinstitute .org/collaboration/giant/index.php/GIANT_consortium. Last modified on the July 18, 2011.
66. Willer CJ, Speliotes EK, Loos RJ, et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41:25-34.
67. Thorleifsson G, Walters GB, Gudbjartsson DF, et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009;41:18-24.
68. Asian Genetic Epidemiology Network. Available from: http://agenconsortium.org/.
69. Kang SJ, Chiang CW, Palmer CD, et al. Genome-wide association of anthropometric traits in African-and African-derived populations. Hum Mol Genet 2010;19:2725-38.
70. Ng MC, Hester JM, Wing MR, et al. Genome-wide association of BMI in African Americans. Obesity 2012;20:622-7.
71. Kilpelainen TO, Zillikens MC, Stancakova A, et al. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nat Genet 2011;43:753-60.
72. Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008;359:2105-20.
73. Boyko EJ, Fujimoto WY, Leonetti DL, et al. Visceral adiposity and risk of type 2 diabetes: A prospective study among Japanese Americans. Diabetes Care 2000;23:465-71.
74. Brochu M, Starling RD, Tchernof A, et al. Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women. J Clin Endocrinol Metab 2000;85:2378-84.
75. Heard-Costa NL, Zillikens MC, Monda KL, et al. NRXN3 is a novel locus for waist circumference: A genome-wide asso-ciation study from the CHARGE Consortium. PLoS Genet 2009;5:e1000539.
76. Lindgren CM, Heid IM, Randall JC, et al. Genome-wide association scan meta-analysis identifies three loci influencing adi-posity and fat distribution. PLoS Genet 2009;5:e1000508.
77. Cho YS, Go MJ, Kim YJ, et al. A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits. Nat Genet 2009;41:527-34.
78. Cohorts for Heart and Aging Research in Genomic Epide-miology. Available from: http://web.chargeconsortium.com/. Last modified on the May 3, 2013.
79. Heid IM, Jackson AU, Randall JC, 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;42:949-60.
80. Fox CS, Liu Y, White CC, et al. Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 2012;8:e1002695.
81. 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:e1361.
82. Meyre D, Delplanque J, Chevre JC, et al. Genome-wide association study for early-onset and morbid adult obesity identi-fies three new risk loci in European populations. Nat Genet 2009;41:157-9.
83. den Hoed M, Luan J, Langenberg C, et al. Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. Int J Obes (Lond)2013;37:191-6.
84. 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:e1000916.
85. Bradfield JP, Taal HR, Timpson NJ, et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet 2012;44:526-31.
86. Cheung CY, Tso AW, Cheung BM, et al. Obesity susceptibility genetic variants identified from recent genome-wide asso-ciation studies: Implications in a Chinese population. J Clin Endocrinol Metab 2010;95:1395-403.
87. Dorajoo R, Blakemore AI, Sim X, et al. Replication of 13 obesity loci among Singaporean Chinese, Malay and Asian-Indian populations. Int J Obes (Lond) 2012;36:159-63.
88. Li H, Kilpelainen TO, Liu C, et al. Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians. Diabetologia 2012;55:981-95.
89. Hassanein MT, Lyon HN, Nguyen TT, et al. Fine mapping of the association with obesity at the FTO locus in African-derived populations. Hum Mol Genet 2010;19:2907-16.
90. 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;59:2980-8.
91. Hallman DM, Friedel VC, Eissa MA, et al. The association of variants in the FTO gene with longitudinal body mass index profiles in non-Hispanic white children and adolescents. Int J Obes (Lond) 2012;36:61-8.
92. 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;19:545-52.
93. Haworth CM, Carnell S, Meaburn EL, et al. Increasing heritability of BMI and stronger associations with the FTO gene over childhood. Obesity (Silver Spring) 2008;16:2663-8.
94. 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:e1746.
95. Ng MC, Tam CH, So WY, et al. Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese. J Clin Endocrinol Metab 2010;95:2418-25.
96. Liu G, Zhu H, Lagou V, et al. Common variants near melanocortin 4 receptor are associated with general and visceral adiposity in European-and African-American youth. J Pediatr 2010;156:598-605 e1.
97. Wu L, Xi B, Zhang M, et al. Associations of six single nucleotide polymorphisms in obesity-related genes with BMI and risk of obesity in Chinese children. Diabetes 2010; 59:3085-9.
98. 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:e1000284.
99. Zhao J, Bradfield JP, Zhang H, et al. Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans. Obesity 2011;19:2436-9.
100. Wang J, Mei H, Chen W, et al. Study of eight GWAS-identified common variants for association with obesity-related indices in Chinese children at puberty. Int J Obes (Lond) 2012;36:542-7.
101. Knowler WC, Pettitt DJ, Saad MF, et al. Obesity in the Pima Indians: Its magnitude and relationship with diabetes. Am J Clin Nutr 1991;53:1543S-51S.
102. Ravussin E, Valencia ME, Esparza J, et al. Effects of a traditional lifestyle on obesity in Pima Indians. Diabetes Care 1994;17:1067-74.
103. Kilpelainen 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:e1001116.
104. Li S, Zhao JH, Luan J, et al. Physical activity attenuates the genetic predisposition to obesity in 20,000 men and women from EPIC-Norfolk prospective population study. PLoS Med 2010;7. e1000332.
105. Gerken T, Girard CA, Tung YC, et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 2007;318:1469-72.
106. Fischer J, Koch L, Emmerling C, et al. Inactivation of the Fto gene protects from obesity. Nature 2009;458:894-8.
107. Boissel S, Reish O, Proulx K, et al. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 2009;85:106-11.
108. den Hoed M, Westerterp-Plantenga MS, Bouwman FG, et al. Postprandial responses in hunger and satiety are associated with the rs9939609 single nucleotide polymorphism in FTO. Am J Clin Nutr 2009;90:1426-32.
109. Speakman JR, Rance KA, Johnstone AM. Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure. Obesity (Silver Spring) 2008;16:1961-5.
110. Wardle J, Carnell S, Haworth CM, et al. Obesity associated genetic variation in FTO is associated with diminished satiety. J Clin Endocrinol Metab 2008;93:3640-3.
111. Tung YC, Ayuso E, Shan X, et al. Hypothalamic-specific manipulation of Fto, the ortholog of the human obesity gene FTO, affects food intake in rats. PLoS One 2010;5:e8771.
112. 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:E181-8.
113. Walters RG, Jacquemont S, Valsesia A, et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature 2010;463:671-5.
114. Mendiratta MS, Yang Y, Balazs AE, et al. Early onset obesity and adrenal insufficiency associated with a homozygous POMC mutation. Int J Pediatr Endocrinol 2011;2011:5.
115. Boesgaard TW, Gjesing AP, Grarup N, et al. Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients-EUGENE2 study. PLoS One 2009;4:e7236.
116. Voight BF, Scott LJ, Steinthorsdottir V, et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 2010;42:579-89.
117. Nishimura S, Manabe I, Nagasaki M, et al. Adipogenesis in obesity requires close interplay between differentiating adipocytes, stromal cells, and blood vessels. Diabetes 2007;56:1517-26.
118. Consortium TGP, Abecasis GR, Altshuler D, et al. A map of human genome variation from population-scale sequencing. Nature 2010;467:1061-73.
119. Bochukova EG, Huang N, Keogh J, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature 2010;463:666-70.
120. Jacquemont S, Reymond A, Zufferey F, et al. Mirror extreme BMI phenotypes associated with gene dosage at the chromosome 16p11.2 locus. Nature 2011;478:97-102.
121. Chen Y, Liu YJ, Pei YF, et al. Copy number variations at the Prader-Willi syndrome region on chromosome 15 and associations with obesity in whites. Obesity 2011;19:1229-34.