Advertisement

The Contribution of Heredity to Clinical Obesity

  • Johanna C. Andersson
  • Andrew J. WalleyEmail author
Chapter
Part of the Endocrine Updates book series (ENDO, volume 30)

Abstract

Obesity has been present in the human population at a low frequency for a very long time, most likely caused by rare monogenic or syndromic genetic disease. In the last few decades of the twentieth century and into the twenty-first, rates of obesity have greatly increased, initially in the USA, then in other Western industrialized countries until we now have a genuinely global epidemic. As evolution works on a far longer timescale than this, it has been concluded by many that genetics cannot possibly play a part in common obesity. However, many studies have demonstrated significant heritability for obesity-related traits, including body mass index (BMI), waist circumference (WC), waist–hip ratio (WHR), and eating behavior. One example would be twin studies of BMI, which have generated heritability estimates of 0.5–0.7 for this trait, commonly used to define clinical obesity. In this chapter we review the evidence for the crucial role of genetics in common clinical obesity within our obesogenic environment. We focus on the role of heritability in common obesity and provide an overview of both study designs and results for different obesity-related traits.

Keywords

Heredity Environment Twin study Adoption study Heritability Obesogenic Linkage Association Case–control Genome-wide 

References

  1. 1.
    James WP. WHO recognition of the global obesity epidemic. Int J Obes (Lond). Dec 2008;32 Suppl 7:S120–6.CrossRefGoogle Scholar
  2. 2.
    Emery EM, Schmid TL, Kahn HS, Filozof PP. A review of the association between abdominal fat distribution, health outcome measures, and modifiable risk factors. Am J Health Promot. May–Jun 1993;7(5):342–53.PubMedCrossRefGoogle Scholar
  3. 3.
    Pischon T, Boeing H, Hoffmann K, et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med. Nov 13 2008;359(20):2105–20.PubMedCrossRefGoogle Scholar
  4. 4.
    Fox CS, Massaro JM, Hoffmann U, et al. Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. Jul 3 2007;116(1):39–48.PubMedCrossRefGoogle Scholar
  5. 5.
    Bell CG, Walley AJ, Froguel P. The genetics of human obesity. Nat Rev Genet. Mar 2005;6(3):221–34.PubMedCrossRefGoogle Scholar
  6. 6.
    Walley AJ, Asher JE, Froguel P. The genetic contribution to non-syndromic human obesity. Nat Rev Genet. Jul 2009;10(7):431–42.PubMedCrossRefGoogle Scholar
  7. 7.
    Poston WS 2nd, Foreyt JP. Obesity is an environmental issue. Atherosclerosis. Oct 1999;146(2):201–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Withers RF. Problems in the genetics of human obesity. Eugen Rev. Jul 1964;56(2):81–90.PubMedGoogle Scholar
  9. 9.
    Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. Jun 26 1997;387(6636):903–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Goldstone AP, Beales PL. Genetic obesity syndromes. Front Horm Res. 2008;36:37–60.PubMedCrossRefGoogle Scholar
  11. 11.
    Visscher PM, Hill WG, Wray NR. Heritability in the genomics era – concepts and misconceptions. Nat Rev Genet. Apr 2008;9(4):255–66.PubMedCrossRefGoogle Scholar
  12. 12.
    Galton F. The history of twins, as a criterion of the relative powers of nature and nurture. Fraser’s Mag. 1875;12:566–76.Google Scholar
  13. 13.
    Siemens HW. Die Zwillingspathologie: Ihre Bedeutng, ihre Methodik, ihre biseherigen Ergebnisse (Twin Pathologies: Its Importance, Its Methodology, Its Previous Results). Berlin: Springer; 1924.Google Scholar
  14. 14.
    Segal NL, Feng R, McGuire SA, Allison DB, Miller S. Genetic and environmental contributions to body mass index: comparative analysis of monozygotic twins, dizygotic twins and same-age unrelated siblings. Int J Obes (Lond). Jan 2009;33(1):37–41.CrossRefGoogle Scholar
  15. 15.
    Bogl LH, Pietilainen KH, Rissanen A, Kaprio J. Improving the accuracy of self-reports on diet and physical exercise: the co-twin control method. Twin Res Hum Genet. Dec 2009;12(6):531–40.PubMedCrossRefGoogle Scholar
  16. 16.
    Leskinen T, Sipila S, Alen M, et al. Leisure-time physical activity and high-risk fat: a longitudinal population-based twin study. Int J Obes (Lond). Nov 2009;33(11):1211–8.CrossRefGoogle Scholar
  17. 17.
    Pietilainen KH, Rissanen A, Laamanen M, et al. Growth patterns in young adult monozygotic twin pairs discordant and concordant for obesity. Twin Res. Oct 2004;7(5):421–9.PubMedGoogle Scholar
  18. 18.
    Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord. Jun 1996;20(6):501–6.PubMedGoogle Scholar
  19. 19.
    Maes HH, Neale MC, Eaves LJ. Genetic and environmental factors in relative body weight and human adiposity. Behav Genet. Jul 1997;27(4):325–51.PubMedCrossRefGoogle Scholar
  20. 20.
    Koeppen-Schomerus G, Wardle J, Plomin R. A genetic analysis of weight and overweight in 4-year-old twin pairs. Int J Obes Relat Metab Disord. Jun 2001;25(6):838–44.PubMedCrossRefGoogle Scholar
  21. 21.
    van Dommelen P, de Gunst MC, van der Vaart AW, Boomsma DI. Genetic study of the height and weight process during infancy. Twin Res. Dec 2004;7(6):607–16.PubMedGoogle Scholar
  22. 22.
    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. Feb 2008;87(2):398–404.PubMedGoogle Scholar
  23. 23.
    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). Dec 2008;16(12):2663–8.CrossRefGoogle Scholar
  24. 24.
    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). May 2009;33(5):559–67.CrossRefGoogle Scholar
  25. 25.
    Brook CG, Huntley RM, Slack J. Influence of heredity and environment in determination of skinfold thickness in children. Br Med J. Jun 28 1975;2(5973):719–21.PubMedCrossRefGoogle Scholar
  26. 26.
    Stunkard AJ, Foch TT, Hrubec Z. A twin study of human obesity. JAMA. Jul 4 1986;256(1):51–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The body-mass index of twins who have been reared apart. N Engl J Med. May 24 1990;322(21):1483–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Gorlova OY, Amos CI, Wang NW, Shete S, Turner ST, Boerwinkle E. Genetic linkage and imprinting effects on body mass index in children and young adults. Eur J Hum Genet. Jun 2003;11(6):425–32.PubMedCrossRefGoogle Scholar
  29. 29.
    Perusse L, Rice T, Chagnon YC, et al. A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study. Diabetes. Mar 2001;50(3):614–21.PubMedCrossRefGoogle Scholar
  30. 30.
    Mitchell BD, Cole SA, Comuzzie AG, et al. A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor. Diabetes. Sep 1999;48(9):1863–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Wilson SG, Adam G, Langdown M, et al. Linkage and potential association of obesity-related phenotypes with two genes on chromosome 12q24 in a female dizygous twin cohort. Eur J Hum Genet. Mar 2006;14(3):340–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Kettunen J, Perola M, Martin NG, et al. Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci. Int J Obes (Lond). Nov 2009;33(11):1235–42.CrossRefGoogle Scholar
  33. 33.
    Haworth CM, Plomin R, Carnell S, Wardle J. Childhood obesity: genetic and environmental overlap with normal-range BMI. Obesity (Silver Spring). Jul 2008;16(7):1585–90.CrossRefGoogle Scholar
  34. 34.
    Lettre G. Genetic regulation of adult stature. Curr Opin Pediatr. Aug 2009;21(4):515–22.PubMedCrossRefGoogle Scholar
  35. 35.
    Silventoinen K, Pietilainen KH, Tynelius P, Sorensen TI, Kaprio J, Rasmussen F. Genetic and environmental factors in relative weight from birth to age 18: the Swedish young male twins study. Int J Obes (Lond). Apr 2007;31(4):615–21.CrossRefGoogle Scholar
  36. 36.
    Silventoinen K, Rokholm B, Kaprio J, Sorensen TI. The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies. Int J Obes (Lond). Jan 2010;34(1):29–40.CrossRefGoogle Scholar
  37. 37.
    Haberstick BC, Lessem JM, McQueen MB, et al. Stable genes and changing environments: body mass index across adolescence and young adulthood. Behav Genet. Jan 20 2010 Jul; 40(4):495–504 (Epub Jan 20, 2010).Google Scholar
  38. 38.
    Duncan AE, Agrawal A, Grant JD, Bucholz KK, Madden PA, Heath AC. Genetic and environmental contributions to BMI in adolescent and young adult women. Obesity (Silver Spring). May 2009;17(5):1040–3.CrossRefGoogle Scholar
  39. 39.
    Pietilainen KH, Kaprio J, Rissanen A, et al. Distribution and heritability of BMI in Finnish adolescents aged 16y and 17y: a study of 4884 twins and 2509 singletons. Int J Obes Relat Metab Disord. Feb 1999;23(2):107–15.PubMedCrossRefGoogle Scholar
  40. 40.
    North KE, Graff M, Adair LS, et al. Genetic epidemiology of BMI and body mass change from adolescence to young adulthood. Obesity (Silver Spring). Oct 22 2010 Jul;18(7):1474–6 (Epub Oct 22, 2009).Google Scholar
  41. 41.
    Hjelmborg JB, Fagnani C, Silventoinen K, et al. Genetic influences on growth traits of BMI: a longitudinal study of adult twins. Obesity (Silver Spring). Apr 2008;16(4):847–52.CrossRefGoogle Scholar
  42. 42.
    Ordonana JR, Rebollo-Mesa I, Gonzalez-Javier F, et al. Heritability of body mass index: a comparison between the Netherlands and Spain. Twin Res Hum Genet. Oct 2007;10(5):749–56.PubMedCrossRefGoogle Scholar
  43. 43.
    McCarthy HD. Body fat measurements in children as predictors for the metabolic syndrome: focus on waist circumference. Proc Nutr Soc. Nov 2006;65(4):385–92.PubMedGoogle Scholar
  44. 44.
    McTigue KM, Hess R, Ziouras J. Obesity in older adults: a systematic review of the evidence for diagnosis and treatment. Obesity (Silver Spring). Sep 2006;14(9):1485–97.CrossRefGoogle Scholar
  45. 45.
    Allison DB, Heshka S, Neale MC, Lykken DT, Heymsfield SB. A genetic analysis of relative weight among 4,020 twin pairs, with an emphasis on sex effects. Health Psychol. Jul 1994;13(4):362–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Bodurtha JN, Mosteller M, Hewitt JK, et al. Genetic analysis of anthropometric measures in 11-year-old twins: the Medical College of Virginia Twin Study. Pediatr Res. Jul 1990;28(1):1–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Malis C, Rasmussen EL, Poulsen P, et al. Total and regional fat distribution is strongly influenced by genetic factors in young and elderly twins. Obes Res. Dec 2005;13(12):2139–45.PubMedCrossRefGoogle Scholar
  48. 48.
    Cardon LR, Carmelli D, Fabsitz RR, Reed T. Genetic and environmental correlations between obesity and body fat distribution in adult male twins. Hum Biol. Jun 1994;66(3):465–79.PubMedGoogle Scholar
  49. 49.
    Carey DG, Nguyen TV, Campbell LV, Chisholm DJ, Kelly P. Genetic influences on central abdominal fat: a twin study. Int J Obes Relat Metab Disord. Aug 1996;20(8):722–6.PubMedGoogle Scholar
  50. 50.
    Bouchard C, Tremblay A. Genetic influences on the response of body fat and fat distribution to positive and negative energy balances in human identical twins. J Nutr. May 1997;127 5 Suppl:943S–7S.PubMedGoogle Scholar
  51. 51.
    Skidmore PM, Cassidy A, Swaminathan R, et al. An obesogenic postnatal environment is more important than the fetal environment for the development of adult adiposity: a study of female twins. Am J Clin Nutr. Aug 2009;90(2):401–6.PubMedCrossRefGoogle Scholar
  52. 52.
    Song TM, Perusse L, Malina RM, Bouchard C. Twin resemblance in somatotype and comparisons with other twin studies. Hum Biol. Jun 1994;66(3):453–64.PubMedGoogle Scholar
  53. 53.
    Reis VM, Machado JV, Fortes MS, et al. Evidence for higher heritability of somatotype compared to body mass index in female twins. J Physiol Anthropol. Jan 2007;26(1):9–14.PubMedCrossRefGoogle Scholar
  54. 54.
    Peeters MW, Thomis MA, Claessens AL, et al. Heritability of somatotype components from early adolescence into young adulthood: a multivariate analysis on a longitudinal twin study. Ann Hum Biol. Jul–Aug 2003;30(4):402–18.PubMedCrossRefGoogle Scholar
  55. 55.
    Peeters MW, Thomis MA, Loos RJ, et al. Heritability of somatotype components: a multivariate analysis. Int J Obes (Lond). Aug 2007;31(8):1295–301.CrossRefGoogle Scholar
  56. 56.
    O’Rahilly S, Farooqi IS. Human obesity: a heritable neurobehavioral disorder that is highly sensitive to environmental conditions. Diabetes. Nov 2008;57(11):2905–10.PubMedCrossRefGoogle Scholar
  57. 57.
    McKinnon RA, Reedy J, Morrissette MA, Lytle LA, Yaroch AL. Measures of the food environment: a compilation of the literature, 1990–2007. Am J Prev Med. Apr 2009;36 4 Suppl: S124–33.PubMedCrossRefGoogle Scholar
  58. 58.
    Sung J, Lee K, Song YM, Lee MK, Lee DH. Heritability of eating behavior assessed using the DEBQ (Dutch Eating Behavior Questionnaire) and weight-related traits: the healthy twin study. Obesity (Silver Spring). Oct 29 2010 May;18(5):1000–5 (Epub Oct 29, 2009).Google Scholar
  59. 59.
    van Strien T, Frijter JER, Bergers GPA, Defares PB. The Dutch Eating Behaviour Questionnaire (DEBQ) for assessment of restrained, emotional and external eating behaviour. Int J Eat Disord. 1986;5:295–315.CrossRefGoogle Scholar
  60. 60.
    Keskitalo K, Tuorila H, Spector TD, et al. The three-factor eating questionnaire, body mass index, and responses to sweet and salty fatty foods: a twin study of genetic and environmental associations. Am J Clin Nutr. Aug 2008;88(2):263–71.PubMedGoogle Scholar
  61. 61.
    Stunkard AJ, Messick S. The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. J Psychosom Res. 1985;29(1):71–83.PubMedCrossRefGoogle Scholar
  62. 62.
    Carnell S, Haworth CM, Plomin R, Wardle J. Genetic influence on appetite in children. Int J Obes (Lond). Oct 2008;32(10):1468–73.CrossRefGoogle Scholar
  63. 63.
    Carnell S, Wardle J. Appetite and adiposity in children: evidence for a behavioral susceptibility theory of obesity. Am J Clin Nutr. Jul 2008;88(1):22–9.PubMedGoogle Scholar
  64. 64.
    Llewellyn CH, van Jaarsveld CH, Boniface D, Carnell S, Wardle J. Eating rate is a heritable phenotype related to weight in children. Am J Clin Nutr. Dec 2008;88(6):1560–6.PubMedCrossRefGoogle Scholar
  65. 65.
    Keski-Rahkonen A, Bulik CM, Pietilainen KH, Rose RJ, Kaprio J, Rissanen A. Eating styles, overweight and obesity in young adult twins. Eur J Clin Nutr. Jul 2007;61(7):822–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Jakicic JM. The effect of physical activity on body weight. Obesity (Silver Spring). Dec 2009;17 Suppl 3:S34–8.CrossRefGoogle Scholar
  67. 67.
    Silventoinen K, Hasselbalch AL, Lallukka T, et al. Modification effects of physical activity and protein intake on heritability of body size and composition. Am J Clin Nutr. Oct 2009;90(4):1096–103.PubMedCrossRefGoogle Scholar
  68. 68.
    McCaffery JM, Papandonatos GD, Bond DS, Lyons MJ, Wing RR. Gene × environment interaction of vigorous exercise and body mass index among male Vietnam-era twins. Am J Clin Nutr. Apr 2009;89(4):1011–8.PubMedCrossRefGoogle Scholar
  69. 69.
    Mustelin L, Silventoinen K, Pietilainen K, Rissanen A, Kaprio J. Physical activity reduces the influence of genetic effects on BMI and waist circumference: a study in young adult twins. Int J Obes (Lond). Jan 2009;33(1):29–36.CrossRefGoogle Scholar
  70. 70.
    Waller K, Kaprio J, Kujala UM. Associations between long-term physical activity, waist circumference and weight gain: a 30-year longitudinal twin study. Int J Obes (Lond). Feb 2008;32(2):353–61.CrossRefGoogle Scholar
  71. 71.
    Joosen AM, Gielen M, Vlietinck R, Westerterp KR. Genetic analysis of physical activity in twins. Am J Clin Nutr. Dec 2005;82(6):1253–9.PubMedGoogle Scholar
  72. 72.
    Hartz A, Giefer E, Rimm AA. Relative importance of the effect of family environment and heredity on obesity. Ann Hum Genet. Oct 1977;41(2):185–93.PubMedCrossRefGoogle Scholar
  73. 73.
    Biron P, Mongeau JG, Bertrand D. Familial resemblance of body weight and weight/height in 374 homes with adopted children. J Pediatr. Oct 1977;91(4):555–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Cardon LR. Genetic influence on body mass index in early childhood. In: Turner JR, Cardon, LR, Hewitt, JK, editors. Behavior genetic approaches in behavioral medicine. New York, NY: Plenum Press; 1995;3–13.Google Scholar
  75. 75.
    Sorensen TI, Holst C, Stunkard AJ. Childhood body mass index – genetic and familial environmental influences assessed in a longitudinal adoption study. Int J Obes Relat Metab Disord. Sep 1992;16(9):705–14.PubMedGoogle Scholar
  76. 76.
    Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med. Jan 23 1986;314(4):193–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Sorensen TI, Price RA, Stunkard AJ, Schulsinger F. Genetics of obesity in adult adoptees and their biological siblings. BMJ. Jan 14 1989;298(6666):87–90.PubMedCrossRefGoogle Scholar
  78. 78.
    Sorensen TI, Holst C, Stunkard AJ, Skovgaard LT. Correlations of body mass index of adult adoptees and their biological and adoptive relatives. Int J Obes Relat Metab Disord. Mar 1992;16(3):227–36.PubMedGoogle Scholar
  79. 79.
    Sorensen TI, Stunkard AJ. Does obesity run in families because of genes? An adoption study using silhouettes as a measure of obesity. Acta Psychiatr Scand Suppl. 1993;370:67–72.PubMedCrossRefGoogle Scholar
  80. 80.
    Vogler GP, Sorensen TI, Stunkard AJ, Srinivasan MR, Rao DC. Influences of genes and shared family environment on adult body mass index assessed in an adoption study by a comprehensive path model. Int J Obes Relat Metab Disord. Jan 1995;19(1):40–5.PubMedGoogle Scholar
  81. 81.
    Cupples LA. Family study designs in the age of genome-wide association studies: experience from the Framingham Heart Study. Curr Opin Lipidol. Apr 2008;19(2):144–50.PubMedCrossRefGoogle Scholar
  82. 82.
    Laird NM, Lange C. Family-based methods for linkage and association analysis. Adv Genet. 2008;60:219–52.PubMedCrossRefGoogle Scholar
  83. 83.
    Young EH, Wareham NJ, Farooqi S, et al. The V103I polymorphism of the MC4R gene and obesity: population based studies and meta-analysis of 29 563 individuals. Int J Obes (Lond). Sep 2007;31(9):1437–41.CrossRefGoogle Scholar
  84. 84.
    Ness R, Laskarzewski P, Price RA. Inheritance of extreme overweight in black families. Hum Biol. Feb 1991;63(1):39–52.PubMedGoogle Scholar
  85. 85.
    Rice T, Borecki IB, Bouchard C, Rao DC. Segregation analysis of fat mass and other body composition measures derived from underwater weighing. Am J Hum Genet. May 1993;52(5):967–73.PubMedGoogle Scholar
  86. 86.
    Rice T, Borecki IB, Bouchard C, Rao DC. Segregation analysis of body mass index in an unselected French-Canadian sample: the Quebec Family Study. Obes Res. Jul 1993;1(4):288–94.PubMedCrossRefGoogle Scholar
  87. 87.
    Lecomte E, Herbeth B, Nicaud V, Rakotovao R, Artur Y, Tiret L. Segregation analysis of fat mass and fat-free mass with age- and sex-dependent effects: the Stanislas Family Study. Genet Epidemiol. 1997;14(1):51–62.PubMedCrossRefGoogle Scholar
  88. 88.
    Borecki IB, Higgins M, Schreiner PJ, et al. Evidence for multiple determinants of the body mass index: the National Heart, Lung, and Blood Institute Family Heart Study. Obes Res. Mar 1998;6(2):107–14.PubMedCrossRefGoogle Scholar
  89. 89.
    Rice T, Sjostrom CD, Perusse L, Rao DC, Sjostrom L, Bouchard C. Segregation analysis of body mass index in a large sample selected for obesity: the Swedish Obese Subjects study. Obes Res. May 1999;7(3):246–55.PubMedCrossRefGoogle Scholar
  90. 90.
    Feitosa MF, Borecki I, Hunt SC, Arnett DK, Rao DC, Province M. Inheritance of the waist-to-hip ratio in the National Heart, Lung, and Blood Institute Family Heart Study. Obes Res. Jul 2000;8(4):294–301.PubMedCrossRefGoogle Scholar
  91. 91.
    Platte P, Papanicolaou GJ, Johnston J, et al. A study of linkage and association of body mass index in the Old Order Amish. Am J Med Genet C Semin Med Genet. Aug 15 2003;121C(1):71–80.PubMedCrossRefGoogle Scholar
  92. 92.
    Magnusson PK, Rasmussen F. Familial resemblance of body mass index and familial risk of high and low body mass index. A study of young men in Sweden. Int J Obes Relat Metab Disord. Sep 2002;26(9):1225–31.PubMedCrossRefGoogle Scholar
  93. 93.
    Davey G, Ramachandran A, Snehalatha C, Hitman GA, McKeigue PM. Familial aggregation of central obesity in Southern Indians. Int J Obes Relat Metab Disord. Nov 2000;24(11):1523–7.PubMedCrossRefGoogle Scholar
  94. 94.
    Steinle NI, Hsueh WC, Snitker S, et al. Eating behavior in the Old Order Amish: heritability analysis and a genome-wide linkage analysis. Am J Clin Nutr. Jun 2002;75(6):1098–106.PubMedGoogle Scholar
  95. 95.
    Henneman P, Aulchenko YS, Frants RR, van Dijk KW, Oostra BA, van Duijn CM. Prevalence and heritability of the metabolic syndrome and its individual components in a Dutch isolate: the Erasmus Rucphen Family study. J Med Genet. Sep 2008;45(9):572–7.PubMedCrossRefGoogle Scholar
  96. 96.
    Smith JG, Newton-Cheh C. Genome-wide association study in humans. Methods Mol Biol. 2009;573:231–58.PubMedCrossRefGoogle Scholar
  97. 97.
    Manolio TA, Collins FS, Cox NJ, et al. Finding the missing heritability of complex diseases. Nature. Oct 8 2009;461(7265):747–53.PubMedCrossRefGoogle Scholar
  98. 98.
    Reich DE, Lander ES. On the allelic spectrum of human disease. Trends Genet. Sep 2001;17(9):502–10.PubMedCrossRefGoogle Scholar
  99. 99.
    Blakemore AI, Meyre D, Delplanque J, et al. A rare variant in the visfatin gene (NAMPT/PBEF1) is associated with protection from obesity. Obesity (Silver Spring). Aug 2009;17(8):1549–53.CrossRefGoogle Scholar
  100. 100.
    Wellcome Trust Case Control Consortium, et al. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Nature. Apr 1 2010;464(7289):713–20.Google Scholar
  101. 101.
    Conrad DF, Pinto D, Redon R, et al. Origins and functional impact of copy number variation in the human genome. Nature. Apr 1 2010;464(7289):704–12.PubMedCrossRefGoogle Scholar
  102. 102.
    Bochukova EG, Huang N, Keogh J, et al. Large, rare chromosomal deletions associated with severe early-onset obesity. Nature. Feb 4 2010;463(7281):666–70.PubMedCrossRefGoogle Scholar
  103. 103.
    Walters RG, Jacquemont S, Valsesia A, et al. A new highly penetrant form of obesity due to deletions on chromosome 16p11.2. Nature. Feb 4 2010;463(7281):671–5.PubMedCrossRefGoogle Scholar
  104. 104.
    Perez-Pastor EM, Metcalf BS, Hosking J, Jeffery AN, Voss LD, Wilkin TJ. Assortative weight gain in mother-daughter and father-son pairs: an emerging source of childhood obesity. Longitudinal study of trios (EarlyBird 43). Int J Obes (Lond). Jul 2009;33(7):727–35.CrossRefGoogle Scholar
  105. 105.
    Ley RE. Obesity and the human microbiome. Curr Opin Gastroenterol. Jan 2010;26(1):5–11.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Genomics of Common Disease, Faculty of MedicineSchool of Public Health, Imperial College London, Hammersmith HospitalLondonUK

Personalised recommendations