1. Stunkard AJ, Foch TT, Hrubec Z 1986 A twin study of human obesity. Jama 256:51-4
2. Maes HH, Neale MC, Eaves LJ 1997 Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 27:325-51
3. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE 1990 The body-mass index of twins who have been reared apart. N Engl J Med 322:1483-7
4. Price RA, Gottesman, II 1991 Body fat in identical twins reared apart: roles for genes and environment. Behav Genet 21:1-7
5. Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K 1996 The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord 20:501-6
6. Stunkard AJ, Sorensen TI, Hanis C, et al. 1986 An adoption study of human obesity. N Engl J Med 314:193-8
7. Sorensen TI, Price RA, Stunkard AJ, Schulsinger F 1989 Genetics of obesity in adult adoptees and their biological siblings. Bmj 298:87-90
8. Karlin S, Williams PT, Jensen S, Farquhar JW 1981 Genetic analysis of the Stanford LRC family study data. I. Structured exploratory data analysis of height and weight measurements. Am J Epidemiol 113:307-24
9. Zonta LA, Jayakar SD, Bosisio M, Galante A, Pennetti V 1987 Genetic analysis of human obesity in an Italian sample. Hum Hered 37:129-39
10. Butler M 1990 Prader-Willi syndrome: current understanding of cause and diagnosis. Am J Med Genet 35:319-32
11. Bray GA DW, Swerdloff RS, Fiser RH, Atkinson RL, Carrel RE. 1983 The Prader-Willi syndrome: a study of 40 patients and a review of the literature. Medicine (Baltimore) 62:59-80
12. Holm VA CS, Butler MG, Hanchett JM, Greenswag LR, Whitman BY, Greenberg F. 1993 Prader-Willi syndrome: consensus diagnostic criteria. Pediatrics 91:398-402
13. Nagai T, Mori M 1999 Prader-Willi syndrome, diabetes mellitus and hypogonadism. Biomed Pharmacother 53:452-4
14. Eiholzer U BW, Molinari L. 1999 Body fat determined by skinfold measurements is elevated despite underweight in infants with Prader-Labhart-Willi syndrome. J Pediatr 134:222-5
15. Butler MG, Moore J, Morawiecki A, Nicolson M 1998 Comparison of leptin protein levels in Prader-Willi syndrome and control individuals. Am J Med Genet 75:7-12
16. Lindgren AC BB, Hagg A, Ritzen EM, Marcus C, Rossner S. 2000 Eating behavior in Prader-Willi syndrome, normal weight, and obese control groups. J Pediatr 137:50-5
17. Tschop M SD, Heiman ML 2000 Ghrelin induces adiposity in rodents. Nature 407:908-13
18. Cummings DE PJ, Frayo RS, Schmidova K, Wisse BE, Weigle DS. 2001 A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50:1714-9
19. Cummings DE WD, Frayo RS, Breen PA, Ma MK, Dellinger EP, Purnell JQ. 2002 Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 346:1623-30
20. Cummings DE CK, Purnell JQ, Vaisse C, Foster KE, Frayo RS, Schwartz MW, Basdevant A, Weigle DS. 2002 Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 8:643-4
21. van Mil EG WK, Gerver WJ, Van Marken Lichtenbelt WD, Kester AD, Saris WH. 2001 Body composition in Prader-Willi syndrome compared with nonsyndromal obesity: Relationship to physical activity and growth hormone function. J Pediatr 139:708-14
22. Carrel AL, Allen DB 2001 Prader-Willi syndrome: how does growth hormone affect body composition and physical function? J Pediatr Endocrinol Metab 14 Suppl 6:1445-51
23. Carrel AL MS, Whitman BY, Allen DB. 1999 Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study. J Pediatr 134:215-21
24. Lindgren AC HL, Ritzen EM, Milerad J. 1999 Growth hormone treatment increases CO(2) response, ventilation and central inspiratory drive in children with Prader-Willi syndrome. Eur J Pediatr 158:936-40
25. Hamilton CR Jr SR, Kliman B. 1972 Hypogonadotropinism in Prader-Willi syndrome. Induction of puberty and sperm altogenesis by clomiphene citrate. Am J Med 52:322-9
26. Ohta T, Gray TA, Rogan PK, et al. 1999 Imprinting-mutation mechanisms in Prader-Willi syndrome. Am J Hum Genet 64:397-413
27. Amos-Landgraf JM JY, Gottlieb W, Depinet T, Wandstrat AE, Cassidy SB, Driscoll DJ, Rogan PK, Schwartz S, Nicholls RD. 1999 Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints. Am J Hum Genet 65:370-86
28. Carrozzo R RE, Christian SL, Kittikamron K, Livieri C, Corrias A, Pucci L, Fois A, Simi P, Bosio L, Beccaria L, Zuffardi O, Ledbetter DH. 1997 Inter- and intrachromosomal rearrangements are both involved in the origin of 15q11-q13 deletions in Prader-Willi syndrome. Am J Hum Genet 61:228-31
29. Charrow J BN, Cohen MM. 1983 Translocations in Prader-Willi syndrome. Clin Genet 23:304-7
30. Driscoll DJ WM, Williams CA, Zori RT, Glenn CC, Avidano KM, Nicholls RD. 1992 A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics 13:917-24
31. Clayton-Smith J, Driscoll DJ, Waters MF, et al. 1993 Difference in methylation patterns within the D15S9 region of chromosome 15q11-13 in first cousins with Angelman syndrome and Prader-Willi syndrome. Am J Med Genet 47:683-6
32. Dittrich B RW, Knoblauch H, Buiting K, Schmidt K, Gillessen-Kaesbach G, Horsthemke B. 1992 Molecular diagnosis of the Prader-Willi and Angelman syndromes by detection of parent-of-origin specific DNA methylation in 15q11-13. Hum Genet 90:313-5
33. Swaab DF, Purba JS, Hofman MA 1995 Alterations in the hypothalamic paraventricular nucleus and its oxytocin neurons (putative satiety cells) in Prader-Willi syndrome: a study of five cases. J Clin Endocrinol Metab 80:573-9
34. Muscatelli F AD, Massacrier A, Boccaccio I, Le Moal M, Cau P, Cremer H. 2000 Disruption of the mouse Necdin gene results in hypothalamic and behavioral alterations reminiscent of the human Prader-Willi syndrome. Hum Mol Genet 9:3101-10
35. MacDonald HR, Wevrick R 1997 The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse. Hum Mol Genet 6:1873-8
36. Buiting K DB, Gross S, Greger V, Lalande M, Robinson W, Mutirangura A, Ledbetter D, Horsthemke B. 1993 Molecular definition of the Prader-Willi syndrome chromosome region and orientation of the SNRPN gene. Hum Mol Genet 2:1991-4
37. Ozcelik T LS, Robinson W, Donlon T, Lalande M, Sanjines E, Schinzel A, Francke U. 1992 Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nat Genet 2:265-9
38. Tsai TF, Jiang YH, Bressler J, Armstrong D, Beaudet AL 1999 Paternal deletion from Snrpn to Ube3a in the mouse causes hypotonia, growth retardation and partial lethality and provides evidence for a gene contributing to Prader-Willi syndrome. Hum Mol Genet 8:1357-64
39. Jong MT, Carey AH, Caldwell KA, et al. 1999 Imprinting of a RING zinc-finger encoding gene in the mouse chromosome region homologous to the Prader-Willi syndrome genetic region. Hum Mol Genet 8:795-803
40. Jong MT, Gray TA, Ji Y, et al. 1999 A novel imprinted gene, encoding a RING zinc-finger protein, and overlapping antisense transcript in the Prader-Willi syndrome critical region. Hum Mol Genet 8:783-93
41. Boccaccio I G-DH, Watrin F, Roeckel N, Lalande M, Muscatelli F. 1999 The human MAGEL2 gene and its mouse homologue are paternally expressed and mapped to the Prader-Willi region. Hum Mol Genet 8:2497-505
42. Lee S KS, Hernandez L, Chamberlain SJ, Brannan CI, Stewart CL, Wevrick R. 2000 Expression and imprinting of MAGEL2 suggest a role in Prader-willi syndrome and the homologous murine imprinting phenotype. Hum Mol Genet 9:1813-9
43. de los Santos T, Schweizer J, Rees CA, Francke U 2000 Small evolutionarily conserved RNA, resembling C/D box small nucleolar RNA, is transcribed from PWCR1, a novel imprinted gene in the Prader-Willi deletion region, which Is highly expressed in brain. Am J Hum Genet 67:1067-82
43.1 Lee S, Walker CL, Karten B, Kuny SL, Tennese AA, O'Neill MA, Wevrick R. 2005 Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Hum Mol Genet 14:627-37
44. Weinstein LS, Chen M, Liu J 2002 Gs(alpha) mutations and imprinting defects in human disease. Ann N Y Acad Sci 968:173-97
45. Weinstein LS, Yu S, Liu J 2002 Analysis of genomic imprinting of Gs alpha gene. Methods Enzymol 344:369-83
46. Kaplan G, Kung M, McClure M, Cronister A 1994 Direct mutation analysis of 495 patients for fragile X carrier status/proband diagnosis. Am J Med Genet 51:501-2
47. de Vries BB FJ, Butler MG, Canziani F, Wesby-van Swaay E, van Hemel JO, Oostra BA, Halley DJ, Niermeijer MF. 1993 Clinical and molecular studies in fragile X patients with a Prader-Willi-like phenotype. J Med Genet 30:761-6
48. Gunay-Aygun M, Cassidy SB, Nicholls RD 1997 Prader-Willi and other syndromes associated with obesity and mental retardation. Behav Genet 27:307-24
49. Schrander-Stumpel C, Gerver WJ, Meyer H, Engelen J, Mulder H, Fryns JP 1994 Prader-Willi-like phenotype in fragile X syndrome. Clin Genet 45:175-80
50. Chakravarti A 1992 Fragile X founder effect? Nat Genet 1:237-8
51. Rousseau F, Heitz D, Biancalana V, et al. 1991 Direct diagnosis by DNA analysis of the fragile X syndrome of mental retardation. N Engl J Med 325:1673-81
52. Rhoads FA, Oglesby AC, Mayer M, Jacobs PA 1982 Marker X syndrome in an oriental family with probable transmission by a normal male. Am J Med Genet 12:205-17
52.1 McConkie-Rosell A, Finucane B, Cronister A, Abrams L, Bennett RL, Pettersen BJ 2005 Genetic counseling for fragile x syndrome: updated recommendations of the national society of genetic counselors. J Genet Couns.14:249-70.
53. Klein D, Ammann F 1969 The syndrome of Laurence-Moon-Bardet-Biedl and allied diseases in Switzerland. Clinical, genetic and epidemiological studies. J Neurol Sci 9:479-513
54. Schachat AP MI 1982 Bardet-Biedl syndrome and related disorders. Arch Ophthalmol 100:285-8
55. Katsanis N, Lupski JR, Beales PL 2001 Exploring the molecular basis of Bardet-Biedl syndrome. Hum Mol Genet 10:2293-9.
56. Katsanis N AS, Badano JL, Eichers ER, Lewis RA, Hoskins BE, Scambler PJ, Davidson WS, Beales PL, Lupski JR. 2001 Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder. Science 293:2256-9
57. Mykytyn K ND, Searby CC, Shastri M, Yen HJ, Beck JS, Braun T, Streb LM, Cornier AS, Cox GF, Fulton AB, Carmi R, Luleci G, Chandrasekharappa SC, Collins FS, Jacobson SG, Heckenlively JR, Weleber RG, Stone EM, Sheffield VC. 2002 Identification of the gene (BBS1) most commonly involved in Bardet-Biedl syndrome, a complex human obesity syndrome. Nat Genet 31:435-8
58 Beales PL.2005 Lifting the lid on Pandora's box: the Bardet-Biedl syndrome. Curr Opin Genet Dev15:315-23.
59
Mykytyn K,
Sheffield VC.
2004 Establishing a connection between cilia and Bardet-Biedl Syndrome. Trends
Mol Med.10:106-9
60. Nishimura DY, Fath M, Mullins RF, Searby C, Andrews M, Davis R, Andorf JL, Mykytyn K, Swiderski RE, Yang B, Carmi R, Stone EM, Sheffield VC.2004 Bbs2-null mice have neurosensory deficits, a defect in social dominance, and retinopathy associated with mislocalization of rhodopsin. Proc Natl Acad Sci U S A. 101:16588-93.
61. Mykytyn K, Mullins RF, Andrews M, Chiang AP, Swiderski RE, Yang B, Braun T, Casavant T, Stone EM, Sheffield VC.2004 Bardet-Biedl syndrome type 4 (BBS4)-null mice implicate Bbs4 in flagella formation but not global cilia assembly. Proc Natl Acad Sci U S A. 101:8664-9.
62. Montague CT, Farooqi IS, Whitehead JP, et al. 1997 Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387:903-8
63. Rau H, Reaves BJ, O'Rahilly S, Whitehead JP 1999 Truncated human leptin (delta133) associated with extreme obesity undergoes proteasomal degradation after defective intracellular transport. Endocrinology 140:1718-23
64. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD 1998 A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18:213-5.
65. Farooqi IS, Keogh JM, Kamath S, et al. 2001 Partial leptin deficiency and human adiposity. Nature 414:34-5
66. Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P 1995 Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 269:546-9
67. Halaas JL, Gajiwala KS, Maffei M, et al. 1995 Weight-reducing effects of the plasma protein encoded by the obese gene [see comments]. Science 269:543-6
68. Pelleymounter MA, Cullen MJ, Baker MB, et al. 1995 Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540-3
69. Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI 1998 Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897-901
70. Farooqi IS, Matarese G, Lord GM, et al. 2002 Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110:1093-103
71. Clement K, Vaisse C, Lahlou N, et al. 1998 A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392:398-401
72. Cowley MA, Pronchuk N, Fan W, Dinulescu DM, Colmers WF, Cone RD 1999 Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron 24:155-63
73. Cowley MA, Smart JL, Rubinstein M, et al. 2001 Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 411:480-4.
74. Yeo GS, Farooqi IS, Challis BG, Jackson RS, O'Rahilly S 2000 The role of melanocortin signalling in the control of body weight: evidence from human and murine genetic models. Qjm 93:7-14.
75. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A 1998 Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19:155-7
76. Krude H, Gruters A 2000 Implications of proopiomelanocortin (POMC) mutations in humans: the POMC deficiency syndrome. Trends Endocrinol Metab 11:15-22
77. Echwald SM, Sorensen TI, Andersen T, Tybjaerg-Hansen A, Clausen JO, Pedersen O 1999 Mutational analysis of the proopiomelanocortin gene in Caucasians with early onset obesity. Int J Obes Relat Metab Disord 23:293-8
78. Challis BG, Pritchard LE, Creemers JW, et al. 2002 A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism. Hum Mol Genet 11:1997-2004
79. Miraglia del Giudice E, Cirillo G, Santoro N, et al. 2001 Molecular screening of the proopiomelanocortin (POMC ) gene in Italian obese children: report of three new mutations. Int J Obes Relat Metab Disord 25:61-7
80. O'Rahilly S, Gray H, Humphreys PJ, et al. 1995 Brief report: impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 333:1386-90
81. Jackson RS, Creemers JW, Ohagi S, et al. 1997 Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16:303-6
82. Huszar D, Lynch CA, Fairchild-Huntress V, et al. 1997 Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88:131-41
83. Yeo GS, Farooqi IS, Aminian S, Halsall DJ, Stanhope RG, O'Rahilly S 1998 A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nat Genet 20:111-2
84. Vaisse C, Clement K, Guy-Grand B, Froguel P 1998 A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nat Genet 20:113-4
85. Gu W, Tu Z, Kleyn PW, et al. 1999 Identification and functional analysis of novel human melanocortin-4 receptor variants. Diabetes 48:635-9
86. Hinney A, Schmidt A, Nottebom K, et al. 1999 Several mutations in the melanocortin-4 receptor gene including a nonsense and a frameshift mutation associated with dominantly inherited obesity in humans. J Clin Endocrinol Metab 84:1483-6
87. Farooqi IS, Yeo GS, Keogh JM, et al. 2000 Dominant and recessive inheritance of morbid obesity associated with melanocortin 4 receptor deficiency. J Clin Invest 106:271-9.
87.1
Larsen LH,
Echwald SM,
Sorensen TI,
Andersen T,
Wulff BS,
Pedersen O.2005
Prevalence of mutations and functional analyses of melanocortin 4 receptor
variants identified among 750 men with juvenile-onset obesity.J Clin Endocrinol
Metab. 90:219-24.
87.2
Yeo GS,
Connie Hung CC,
Rochford J,
Keogh J,
Gray J,
Sivaramakrishnan S,
O'Rahilly S,
Farooqi IS.2004
A de novo mutation affecting human TrkB associated with severe obesity and
developmental delay. Nat Neurosci. 7:1187-9.
88. Kristensen P, Judge ME, Thim L, et al. 1998 Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 393:72-6
89. Challis BG YG, Farooqi IS, Luan J, Aminian S, Halsall DJ, Keogh JM, Wareham NJ, O'Rahilly S. 2000 The CART gene and human obesity: mutational analysis and population genetics. Diabetes 49:872-5
90. del Giudice EM, Santoro N, Cirillo G, D'Urso L, Di Toro R, Perrone L 2001 Mutational screening of the CART gene in obese children: identifying a mutation (Leu34Phe) associated with reduced resting energy expenditure and cosegregating with obesity phenotype in a large family. Diabetes 50:2157-60
91. Holder JL, Jr., Butte NF, Zinn AR 2000 Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum Mol Genet 9:101-8
92. Michaud JL, Boucher F, Melnyk A, et al. 2001 Sim1 haploinsufficiency causes hyperphagia, obesity and reduction of the paraventricular nucleus of the hypothalamus. Hum Mol Genet 10:1465-73
93. Farooqi IS, O'Rahilly S 2000 Recent advances in the genetics of severe childhood obesity. Arch Dis Child 83:31-4.
94. Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR 1998 Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 339:953-9
95. Comuzzie AG, Allison DB 1998 The search for human obesity genes. Science 280:1374-7
96. Flint J, Mott R 2001 Finding the molecular basis of quantitative traits: successes and pitfalls. Nat Rev Genet 2:437-45
97. Spielman RS EW 1996 The TDT and other family-based tests for linkage disequilibrium and association. Am J Hum Genet 59:983-9
98. Spielman RS MR, Ewens WJ. 1993 Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus. Am J Hum Genet 52:506-16
99. Spielman RS EW 1998 A sibship test for linkage in the presence of association: The sib transmission/disequilibrium test. Am J Hum Genet 62:450-8
100. Barsh GS, Farooqi IS, O'Rahilly S 2000 Genetics of body-weight regulation. Nature 404:644-51.
101. Comuzzie AG, Hixson JE, Almasy L, et al. 1997 A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nat Genet 15:273-6
102. Hager J, Dina C, Francke S, et al. 1998 A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet 20:304-8
103. Rotimi CN, Comuzzie AG, Lowe WL, Luke A, Blangero J, Cooper RS 1999 The quantitative trait locus on chromosome 2 for serum leptin levels is confirmed in African-Americans. Diabetes 48:643-4
104. Hixson JE, Almasy L, Cole S, et al. 1999 Normal variation in leptin levels in associated with polymorphisms in the proopiomelanocortin gene, POMC. J Clin Endocrinol Metab 84:3187-91
105. Lindi VI, Uusitupa MI, Lindstrom J, et al. 2002 Association of the Pro12Ala polymorphism in the PPAR-gamma2 gene with 3-year incidence of type 2 diabetes and body weight change in the Finnish Diabetes Prevention Study. Diabetes 51:2581-6
106. Meirhaeghe A FL, Helbecque N, Cottel D, Auwerx J, Deeb SS, Amouyel P. 2000 Impact of the Peroxisome Proliferator Activated Receptor gamma2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes Relat Metab Disord 24:195-9
107. Hara K, Okada T, Tobe K, et al. 2000 The Pro12Ala polymorphism in PPAR gamma2 may confer resistance to type 2 diabetes. Biochem Biophys Res Commun 271:212-6
108. Luan J, Browne PO, Harding AH, et al. 2001 Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes 50:686-9
109. Meirhaeghe A HN, Cottel D, Amouyel P. 1999 Beta2-adrenoceptor gene polymorphism, body weight, and physical activity. Lancet 353:896
110. Meirhaeghe A HN, Cottel D, Amouyel P. 2000 Impact of polymorphisms of the human beta2-adrenoceptor gene on obesity in a French population. Int J Obes Relat Metab Disord 24:382-7
111. Meirhaeghe A, Luan J, Selberg-Franks P, et al. 2001 The effect of the Gly16Arg polymorphism of the beta(2)-adrenergic receptor gene on plasma free fatty acid levels is modulated by physical activity. J Clin Endocrinol Metab 86:5881-7
112. Risch N MK 1996 The future of genetic studies of complex human diseases. Science 273:1516-7
113. Risch N, Merikangas K 1996 The future of genetic studies of complex human diseases. Science 273:1516-7.
114. Risch N 2000 Searching for genetic determinants in the new millennium. Nature 405:847-56
115. Risch N TJ 1997 Design and analysis of linkage disequililbrium studies for complex human diseases. Hum Genet 61:1707
116. Cardon LR BJ 2001 Association study designs for complex diseases. Nat Rev Genet 2:91-9
117. Bamshad M, Krakowiak PA, Watkins WS, Root S, Carey JC, Jorde LB 1995 A gene for ulnar-mammary syndrome maps to 12q23-q24.1. Hum Mol Genet 4:1973-7
118. Collin GB, Marshall JD, Cardon LR, Nishina PM 1997 Homozygosity mapping at Alstrom syndrome to chromosome 2p. Hum Mol Genet 6:213-9
119. Collin GB, Marshall JD, Ikeda A, et al. 2002 Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alstrom syndrome. Nat Genet 31:74-8
120. Tahvanainen E NR, Karila E, Ranta S, Weissenbach J, Sistonen P, de la Chapelle A. 1994 Cohen syndrome gene assigned to the long arm of chromosome 8 by linkage analysis. Nat Genet 7:201-4
121. Turner G, Gedeon A, Mulley J, et al. 1989 Borjeson-Forssman-Lehmann syndrome: clinical manifestations and gene localization to Xq26-27. Am J Med Genet 34:463-9
122. Steinmuller R, Steinberger D, Muller U 1998 MEHMO (mental retardation, epileptic seizures, hypogonadism and -genitalism, microcephaly, obesity), a novel syndrome: assignment of disease locus to xp21.1-p22.13. Eur J Hum Genet 6:201-6
123. Brzustowicz LM, Farrell S, Khan MB, Weksberg R 1999 Mapping of a new SGBS locus to chromosome Xp22 in a family with a severe form of Simpson-Golabi-Behmel syndrome. Am J Hum Genet 65:779-83
124. Wilson M, Mulley J, Gedeon A, Robinson H, Turner G 1991 New X-linked syndrome of mental retardation, gynecomastia, and obesity is linked to DXS255. Am J Med Genet 40:406-13
125. Thompson DB, Ravussin E, Bennett PH, Bogardus C 1997 Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians. Hum Mol Genet 6:675-9.
126. Chagnon YC CW, Perusse L, Chagnon M, Leibel RL, Bouchard C. 1999 Linkages and associations between the leptin receptor (LEPR) gene and human body composition in the Quebec Family Study. Int J Obes Relat Metab Disord 23:278-86
127. Roth H KT, Rosenkranz K, Hinney A, Ziegler A, Kunz J, Siegfried W, Mayer H, Hebebrand J, Grzeschik KH. 1998 Transmission disequilibrium and sequence variants at the leptin receptor gene in extremely obese German children and adolescents. Hum Genet 103:540-6
128. Chagnon YC, Wilmore JH, Borecki IB, et al. 2000 Associations between the leptin receptor gene and adiposity in middle-aged Caucasian males from the HERITAGE family study. J Clin Endocrinol Metab 85:29-34.
129. Rosmond R CY, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Bjorntorp P. 2000 Hypertension in obesity and the leptin receptor gene locus. J Clin Endocrinol Metab 85:3126-31
130. Wauters M MI, Chagnon M, Rankinen T, Considine RV, Chagnon YC, Van Gaal LF, Bouchard C. 2001 Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women. Int J Obes Relat Metab Disord 25:714-20
131. Yiannakouris N YM, Melistas L, Chan JL, Klimis-Zacas D, Mantzoros CS. 2001 The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability. J Clin Endocrinol Metab 86:4434-9
132. Mammes O AR, Betoulle D, Pean F, Herbeth B, Visvikis S, Siest G, Fumeron F. 2001 LEPR gene polymorphisms: associations with overweight, fat mass and response to diet in women. Eur J Clin Invest 31:398-404
133. Quinton ND LA, Ross RJ, Eastell R, Blakemore AI. 2001 A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women. Hum Genet 108:233-6
134. Del Giudice EM CG, Santoro N et al. 2001 Molecular screening of the proopiomelanocortin (POMC) gene in Italian obese children: report of three new mutations. Int J Obes Relat Metab Disord 25:61-7
135. Ukkola O RE, Jacobson P, Snyder EE, Chagnon M, Sjostrom L, Bouchard C. 2001 Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab 86:3996-9
136. Jenkinson CP CK, Walder K, Herzog H, Hanson, Ravussin E. 2000 Novel polymorphisms in the neuropeptide-Y Y5 receptor associated with obesity in Pima Indians. Int J Obes Relat Metab Disord 24:580-4
137. Chagnon YC CW, Perusse L, Chagnon M, Nadeau A, Wilkison WO, Bouchard C. 1997 Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec Family Study. Mol Med 3:663-73
138. Funakoshi A MK, Matsumoto H, Yamamori S, Takiguchi S, Kataoka K, Takata Y, Matsusue K, Kono A, Shimokata H. 2000 Gene structure of human cholecystokinin (CCK) type-A receptor: body fat content is related to CCK type-A receptor gene promoter polymorphism. FEBS 466:264-6
139. Large V HL, Reynisdottir S, Lonnqvist F, Eriksson P, Lannfelt L, Arner P. 1997 Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function. J Clin Invest 100:3005-13
140. Ishiyama-Shigemoto S YK, Yuan X, Ichikawa F, Nonaka K. 1999 Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus. Diabetologia 42:98-101
141. Yamada K I-SS, Ichikawa F, Yuan X, Koyanagi A, Koyama W, Nonaka K. 1999 Polymorphism in the 5'-leader cistron of the beta2-adrenergic receptor gene associated with obesity and type 2 diabetes. J Clin Endocrinol Metab 84:1754-7
142. Mori Y K-MH, Ito Y, Katakura T, Yasuda K, Ishiyama-Shigemoto S, Yamada K, Akanuma Y, Ohashi Y, Kimura S, Yazaki Y, Kadowaki T. 1999 The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men. Biochem Biophys Res Commun 258:138-40
143. Ukkola O RT, Weisnagel SJ, Sun G, Perusse L, Chagnon YC, Despres JP, Bouchard C. 2000 Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec Family Study. Metabolism 49:1063-70
144. Ehrenborg E SJ, Ruotolo G, Large V, Eriksson P, Arner P, Hamsten A. 2000 The Q/E27 polymorphism in the beta2-adrenoceptor gene is associated with increased body weight and dyslipoproteinaemia involving triglyceride-rich lipoproteins. J Intern Med 247:651-6
145. Rosmond R UO, Chagnon M, Bouchard C, Bjorntorp P. 2000 Polymorphisms of the beta2-adrenergic receptor gene (ADRB2) in relation to cardiovascular risk factors in men. J Intern Med 248:239-44
146. Meirhaeghe A FL, Helbecque N, Cottel D, Lebel P, Dallongeville J, Deeb S, Auwerx J, Amouyel P. 1998 A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans. Hum Mol Genet 7:435-40
147. Deeb SS FL, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J. 1998 A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20:284-7
148. Ek J US, Sorensen TI, Andersen T, Auwerx J, Pedersen O. 1999 Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men. Diabetologia 42:892-5
149. Valve R SK, Miettinen R, Pihlajamaki J, Rissanen A, Deeb SS, Auwerx J, Uusitupa M, Laakso M. 1999 Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women. J Clin Endocrinol Metab 84:3708-12
150. Vaccaro O MF, Ruffa G, Sabatino L, Colantuoni V, Riccardi G. 2000 Pro12Ala mutation in the peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and severe obesity: a case-control study. Int J Obes Relat Metab Disord 24:1195-9
151. Cole SA MB, Hsueh WC, Pineda P, Beamer BA, Shuldiner AR, Comuzzie AG, Blangero J, Hixson JE. 2000 The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with measures of obesity in Mexican Americans. Int J Obes Relat Metab Disord 24:522-4
152. Nicklas BJ, van Rossum EF, Berman DM, Ryan AS, Dennis KE, Shuldiner AR 2001 Genetic variation in the peroxisome proliferator-activated receptor-gamma2 gene (Pro12Ala) affects metabolic responses to weight loss and subsequent weight regain. Diabetes 50:2172-6
153. Hasstedt SJ, Ren QF, Teng K, Elbein SC 2001 Effect of the peroxisome proliferator-activated receptor-gamma 2 pro(12)ala variant on obesity, glucose homeostasis, and blood pressure in members of familial type 2 diabetic kindreds. J Clin Endocrinol Metab 86:536-41
154. Lindi V, Sivenius K, Niskanen L, Laakso M, Uusitupa MI 2001 Effect of the Pro12Ala polymorphism of the PPAR-gamma2 gene on long-term weight change in Finnish non-diabetic subjects. Diabetologia 44:925-6
154.1
Meyre D,
Bouatia-Naji N,
Tounian A,
Samson C,
Lecoeur C,
Vatin V,
Ghoussaini M,
Wachter C,
Hercberg S,
Charpentier G,
Patsch W,
Pattou F,
Charles MA,
Tounian P,
Clement K,
Jouret B,
Weill J,
Maddux BA,
Goldfine ID,
Walley A,
Boutin P,
Dina C,
Froguel P.2005
Variants of ENPP1 are associated with childhood and adult obesity and increase
the risk of glucose intolerance and type 2 diabetes.
Nat Genet. 37:863-7.
155. Buemann B VM, Chagnon M, Chagnon YC, Gagnon J, Perusse L, Dionne F, Despres JP, Tremblay A, Nadeau A, Bouchard C. 1997 Abdominal visceral fat is associated with a BclI restriction fragment length polymorphism at the glucocorticoid receptor gene locus. Obes Res 5:186-92
156. Perusse L, Rice T, Chagnon YC, Despres JP, Lemieux S, Roy S, Lacaille M, Ho-Kim MA, Chagnon M, Province MA, Rao DC, Bouchard C.2001 A genome-wide scan for abdominal fat assessed by computed tomography in the Quebec Family Study.Diabetes. 50:614-21.
157
Meyre D,
Lecoeur C,
Delplanque J,
Francke S,
Vatin V,
Durand E,
Weill J,
Dina C,
Froguel P.2004
A genome-wide scan for childhood obesity-associated traits in French families
shows significant linkage on chromosome 6q22.31-q23.2. Diabetes. 53:803-11.
158
An P,
Teran-Garcia M,
Rice T,
Rankinen T,
Weisnagel SJ,
Bergman RN,
Boston RC,
Mandel S,
Stefanovski D,
Leon AS,
Skinner JS,
Rao DC,
Bouchard C.2005
Genome-wide linkage scans for prediabetes phenotypes in response to 20 weeks of
endurance exercise training in non-diabetic whites and blacks: the HERITAGE
Family Study Diabetologia. 48:1142-9.
159 Stone S, Abkevich V, Hunt SC, Gutin A, Russell DL, Neff CD, Riley R, Frech GC, Hensel CH, Jammulapati S, Potter J, Sexton D, Tran T, Gibbs D, Iliev D, Gress R, Bloomquist B, Amatruda J, Rae PM, Adams TD, Skolnick MH, Shattuck D. 2002 A major predisposition locus for severe obesity, at 4p15-p14. Am J Hum Genet. 70:1459-68.
160
Arya R,
Duggirala R,
Jenkinson CP,
Almasy L,
Blangero J,
O'Connell P,
Stern MP.2004
Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in
Mexican Americans. Am J Hum Genet. 74:272-82.
161
Bell CG,
Benzinou M,
Siddiq A,
Lecoeur C,
Dina C,
Lemainque A,
Clement K,
Basdevant A,
Guy-Grand B,
Mein CA,
Meyre D,
Froguel P.
2004 Genome-wide linkage analysis for severe obesity in french caucasians finds
significant susceptibility locus on chromosome 19q. Diabetes. 53:1857-65.
162
Ohman M,
Oksanen L,
Kaprio J,
Koskenvuo M,
Mustajoki P,
Rissanen A,
Salmi J,
Kontula K,
Peltonen L.
2005 Genome-wide scan of obesity in Finnish sibpairs reveals linkage to
chromosome Xq24. J Clin Endocrinol Metab. 2000 85:3183-90.
163
Suviolahti E,
Oksanen LJ,
Ohman M,
Cantor RM,
Ridderstrale M,
Tuomi T,
Kaprio J,
Rissanen A,
Mustajoki P,
Jousilahti P,
Vartiainen E,
Silander K,
Kilpikari R,
Salomaa V,
Groop L,
Kontula K,
Peltonen L,
Pajukanta P.2003
The SLC6A14 gene shows evidence of association with obesity J Clin Invest.
112:1762-72.