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Genetics of human obesity

  • Karine Clément (a1)
  • DOI:
  • Published online: 01 March 2007

The rapid development of new concepts and tools has led to a change in the way in which researchers carry out nutrition-related research. Obesity is determined by the interaction between predisposing genetic and environmental aspects, but at present the gene–gene and gene–environment interactions contributing to the development of this complex disease cannot be analysed in detail. The purpose of the present paper is to provide some examples of the knowledge that is available in the field of obesity genetics, and also the new strategies being developed that are aimed at studying the relative contribution of numerous genes to obesity and their responses to environmental changes. In the rare cases of monogenic obesities in which a major gene is the cause the molecular approach has proved extremely powerful in the identification of the genes responsible and in defining new syndromes. However, in the common forms of obesity (polygenic obesity) most studies have analysed genotype–phenotype associations without sometimes taking into account the influence of environmental factors (diet, sedentary lifestyle). Among the aspects limiting this integrated approach to obesity are the difficulty of having large enough samples and the expansion of biocomputing tools developed for accessing the question of multiple interactions with no a priori hypotheses. This picture is rapidly changing. Large databases of clinical data and DNA and biological sample banks with more precise environmental information and patient phenotypes are being compiled. The capacity for studying multiple genes simultaneously at the DNA or RNA levels is also possible. Finally, the tremendous progress in biocomputing will allow the integration of these different types of data (relating to environment, phenotype, genotype, gene expression) and will improve the ability to deal with this complex disease.

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Corresponding author: Dr Karine Clément, fax +33 1 40 51 00 57, email
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KG Ardlie , KL Lunetta & M Seielstad (2002) Testing for population subdivision and association in four case-control studies. American Journal of Human Genetics 71, 304311.

R Arya , R Duggirala , CP Jenkinson , L Almasy , J Blangero , P O'Connell & MP Stern (2004) Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican Americans. American Journal of Human Genetics 74, 272282.

KG Becker (2004) The common variants/multiple disease hypothesis of common complex genetic disorders. Medical Hypotheses 62, 309317.

CG Bell , M Benzinou , A Siddiq , C Lecoeur , C Dina & A Lemainque . (2004) Genome-wide linkage analysis for severe obesity in French Caucasians finds significant susceptibility locus on chromosome 19q. Diabetes 53, 18571865.

M Bennermo , C Held , S Stemme , CG Ericsson , A Silveira , F Green & P Tornvall (2004) Genetic predisposition of the interleukin-6 response to inflammation: implications for a variety of major diseases. Clinical Chemistry 50, 21362140.

P Boutin , C Dina , F Vasseur , S Dubois , L Corset , K Seron . (2003) GAD2 on chromosome 10p12 is a candidate gene for human obesity. PLoS Biology 1 E68.

R Branson , N Potoczna , JG Kral , KU Lentes , MR Hoehe & FF Horber (2003) Binge eating as a major phenotype of melanocortin 4 receptor gene mutations. New England Journal of Medicine 348, 10961103.

K Clement & P Ferre (2003) Genetics and the pathophysiology of obesity. Pediatric Research 53, 721725.

RD Cone (2000) The melanocortin-4 receptor.In The Melanocortin Receptors 405448NJ, Totowa: Humana Press.

A Dempfle , A Hinney , M Heinzel-Gutenbrunner , M Raab , F Geller , T Gudermann , H Schafer & J Hebebrand (2004) Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index (letter). Journal of Medical Genetics 41, 795800.

C Dong , Li WD , D Li & RA Price (2005) Interaction between obesity-susceptibility loci in chromosome regions 2p25-p24 and 13 q13-q21. European Journal of Human Genetics 13, 102108.

B Dubern , K Clement , V Pelloux , P Froguel , JP Girardet , B Guy-Grand & P Tounian (2001) Mutational analysis of melanocortin-4 receptor, agouti-related protein, and alpha-melanocyte-stimulating hormone genes in severely obese children. Journal of Pediatrics 139, 204209.

Y Fan , MA Esmail , SJ Ansley , OE Blacque , K Boroevich , AJ Ross . (2004) Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nature Genetics 36, 989993.

IS Farooqi , JM Keogh , S Kamath , S Jones , WT Gibson , R Trussell , SA Jebb , GY Lip , S O'Rahilly (2001) Partial leptin deficiency and human adiposity. Nature 414, 3435.

IS Farooqi , JM Keogh , GS Yeo , EJ Lank , T Cheetham , S O'Rahilly (2003a) Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. New England Journal of Medicine 348, 10851095.

IS Farooqi , G Matarese , GM Lord , JM Keogh , E Lawrence , C Agwu . (2002) Beneficial effects of leptin on obesity T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. Journal of Clinical Investigation 110, 10931103.

IS Farooqi , S O'Rahilly (2004) Monogenic human obesity syndromes. Recent Progress in Hormone Research 59, 409424.

IS Farooqi , GS Yeo , JM Keogh , S Aminian , SA Jebb , G Butler , T Cheetham , S O'Rahilly (2000) Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. Journal of Clinical Investigation 106, 271279.

MF Feitosa , IB Borecki , SS Rich , DK Arnett , P Sholinsky , RH Myers , M Leppert & MA Province (2002) Quantitative-trait loci influencing body-mass index reside on chromosomes 7 and 13: the National Heart Lung, and Blood Institute Family Heart Study. American Journal of Human Genetics 70, 7282.

CE Flodmark , I Lissau , LA Moreno , A Pietrobelli & K Widhalm (2004) New insights into the field of children and adolescents' obesity: the European perspective. International Journal of Obesity and Related Metabolic Disorders 28, 11891196.

J Hebebrand , S Friedel , N Schauble , F Geller & A Hinney (2003) Perspectives: molecular genetic research in human obesity. Obesity Reviews 4, 139146.

J Hebebrand , F Geller , A Dempfle , M Heinzel-Gutenbrunner , M Raab , G Gerber . (2004) Binge-eating episodes are not characteristic of carriers of melanocortin-4 receptor gene mutations. Molecular Psychiatry 9, 796800.

BT Heijmans , AL Beem , G Willemsen , D Posthuma , PE Slagboom & D Boomsma (2004) Further evidence for a QTL influencing body mass index on chromosome 7p from a genome-wide scan in Dutch families. Twin Research 7, 192196.

A Hinney , A Schmidt , K Nottebom , O Heibult , I Becker , A Ziegler . (1999) Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. Journal of Clinical Endocrinology and Metabolism 84, 14831486.

J Hoh & J Ott (2004) Genetic dissection of diseases: design and methods. Current Opinion in Genetics and Development 14, 229232.

D Huszar , CA Lynch , V Fairchild-Huntress , JH Dunmore , Q Fang , LR Berkemeier . (1997) Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131141.

RS Jackson , JW Creemers , IS Farooqi , ML Raffin-Sanson , A Varro , GJ Dockray . (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. Journal of Clinical Investigation 112, 15501560.

RS Jackson , JW Creemers , S Ohagi , ML Raffin-Sanson , L Sanders , CT Montague , JC Hutton , S O'Rahilly (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nature Genetics 16, 303306.

P Jacobson , O Ukkola , T Rankinen , EE Snyder , AS Leon , DC Rao . (2002) Melanocortin 4 receptor sequence variations are seldom a cause of human obesity: the Swedish Obese Subjects, the HERITAGE Family Study, and a Memphis cohort. Journal of Clinical Endocrinology and Metabolism 87, 44424446.

Y Jiang , JB Wilk , I Borecki , S Williamson , AL DeStefano , G Xu , J Liu , RC Ellison , M Province & RH Myers (2004) Common variants in the 5' region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study. American Journal of Human Genetics 75, 220230.

N Katsanis , SJ Ansley , JL Badano , ER Eichers , RA Lewis , BE Hoskins , PJ Scambler , WS Davidson , PL Beales & JR Lupski (2001a) Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293, 22562259.

N Katsanis , JR Lupski & PL Beales (2001b) Exploring the molecular basis of Bardet-Biedl syndrome. Human Molecular Genetics 10, 22932299.

H Krude , H Biebermann , W Luck , R Horn , G Brabant & A Gruters (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nature Genetics 19, 155157.

ES Lander (1996) The new genomics: global views of biology. Science 274, 536539.

LH Larsen , SM Echwald , TI Sorensen , T Andersen , BS Wulff & O Pedersen (2005) Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity. Journal of Clinical Endocrinology and Metabolism 90, 219224.

C Lubrano-Berthelier , E Durand , B Dubern , A Shapiro , P Dazin , J Weill , C Ferron , P Froguel & C Vaisse (2003) Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Human Molecular Genetics 12, 145153.

C Lubrano-Berthelier , C Le Stunff , P Bougneres & C Vaisse (2004) A homozygous null mutation delineates the role of the melanocortin-4 receptor in humans. Journal of Clinical Endocrinology and Metabolism 89, 20282032.

Del Miraglia , E Giudice , G Cirillo , V Nigro , N Santoro , L D'Urso , P Raimondo , D Cozzolino , D Scafato & L Perrone (2002) Low frequency of melanocortin-4 receptor (MC4R) mutations in a Mediterranean population with early-onset obesity. International Journal of Obesity and Related Metabolic Disorders 26, 647651.

WA Nijenhuis , J Oosterom & RA Adan (2001) AgRP(83–132) acts as an inverse agonist on the human-melanocortin-4 receptor. Molecular Endocrinology 15, 164171.

JK Pritchard (2001) Are rare variants responsible for susceptibility to complex diseases. American Journal of Human Genetics 69, 124137.

K Saar , F Geller , F Ruschendorf , A Reis , S Friedel , N Schauble . (2003) Genome scan for childhood and adolescent obesity in German families. Pediatrics 111, 321327.

AM Slavotinek , C Searby , L Al-Gazali , RC Hennekam , C Schrander-Stumpel , M Orcana-Losa . (2002) Mutation analysis of the MKKS gene in McKusick-Kaufman syndrome and selected Bardet-Biedl syndrome patients. Human Genetics 110, 561567.

EE Snyder , B Walts , L Perusse , YC Chagnon , SJ Weisnagel , T Rankinen & C Bouchard (2004) The human obesity gene map: the 2003 update. Obesity Research 12, 369439.

S Srinivasan , C Lubrano-Berthelier , C Govaerts , F Picard , P Santiago , BR Conklin & C Vaisse (2004) Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans. Journal of Clinical Investigation 114, 11581164.

M Stefan & RD Nicholls (2004) What have rare genetic syndromes taught us about the pathophysiology of the common forms of obesity. Current Diabetes Reports 4, 143150.

AJ Stunkard , JR Harris , NL Pedersen & GE McClearn (1990) The body-mass index of twins who have been reared apart. New England Journal of Medicine 322, 14831487.

E Suviolahti , LJ Oksanen , M Ohman , RM Cantor , M Ridderstrale , T Tuomi . (2003) The SLC6A14 gene shows evidence of association with obesity. Journal of Clinical Investigation 112, 17621772.

C Vaisse , K Clement , E Durand , S Hercberg , B Guy-Grand & P Froguel (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. Journal of Clinical Investigation 106, 253262.

C Vaisse , K Clement , B Guy-Grand & P Froguel (1998) A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genetics 20, 113114.

I Wernstedt , AL Eriksson , A Berndtsson , J Hoffstedt , S Skrtic , T Hedner , LM Hulten , O Wiklund , C Ohlsson & JO Jansson (2004) A common polymorphism in the interleukin-6 gene promoter is associated with overweight. International Journal of Obesity and Related Metabolic Disorders 28, 12721279.

JK Wolford , PB Colligan , JD Gruber & C Bogardus (2003) Variants in the interleukin 6 receptor gene are associated with obesity in Pima Indians. Molecular Genetics and Metabolism 80, 338343.

B Xu , EH Goulding , K Zang , D Cepoi , RD Cone , KR Jones , LH Tecott & LF Reichardt (2003) Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nature Neuroscience 6, 736742.

GS Yeo , Hung Connie , Rochford CC , Keogh J , Gray J , Sivaramakrishnan J , S O'Rahilly , IS Farooqi (2004) A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nature Neuroscience 7, 11871189.

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