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Human genetics illuminates the paths to metabolic disease

Nature volume 462, pages 307–314 (2009)Cite this article

Abstract

Metabolic diseases represent a growing threat to world-wide public health. In general, these disorders result from the interaction of heritable factors with environmental influences. Here, I will focus on two important metabolic disorders, namely type 2 diabetes and obesity, and explore the extent to which human molecular genetic research has illuminated our understanding of their underlying pathophysiological mechanisms.

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References

  1. Maes, H. H., Neale, M. C. & Eaves, L. J. Genetic and environmental factors in relative body weight and human adiposity. Behav. Genet. 27, 325–351 (1997)

    Google Scholar 

  2. Poulsen, P., Kyvik, K. O., Vaag, A. & Beck-Nielsen, H. Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance – a population-based twin study. Diabetologia 42, 139–145 (1999)

    Google Scholar 

  3. Wild, S. et al. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27, 1047–1053 (2004)

    Google Scholar 

  4. Wardle, J., Carnell, S., Haworth, C. M. & Plomin, R. Evidence for a strong genetic influence on childhood adiposity despite the force of the obesogenic environment. Am. J. Clin. Nutr. 87, 398–404 (2008)

    Google Scholar 

  5. Pearson, E. R. et al. Switching from insulin to oral sulphonylureas in patients with diabetes due to Kir6.2 mutations. N. Engl. J. Med. 355, 467–477 (2006)Describes dramatic clinical benefits resulting from identification of a specific molecular subtype of diabetes.

    Google Scholar 

  6. Farooqi, I. S. et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J. Clin. Invest. 110, 1093–1103 (2002)Describes reversal of severe human obesity in congenital leptin deficiency by administration of recombinant leptin.

    Google Scholar 

  7. World Health Organization Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF Consultation. 〈http://www.idf.org/webdata/docs/WHO_IDF_definition_diagnosis_of_diabetes.pdf〉 (2006)

  8. Petersen, K. F. & Shulman, G. I. Etiology of insulin resistance. Am. J. Med. 119, S10–S16 (2006)

    Google Scholar 

  9. Reaven, G. M. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37, 1595–1607 (1988)

    Google Scholar 

  10. Cline, G. W. et al. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N. Engl. J. Med. 341, 240–246 (1999)

    Google Scholar 

  11. Turner, R. C. et al. Pathogenesis of NIDDM—a disease of deficient insulin secretion. Baillieres Clin. Endocrinol. Metab. 2, 327–342 (1988)

    Google Scholar 

  12. Tattersall, R. Maturity-onset diabetes of the young: a clinical history. Diabet. Med. 15, 11–14 (1998)

    Google Scholar 

  13. Vionnet, N. et al. Nonsense mutation in the glucokinase gene causes early-onset non-insulin-dependent diabetes mellitus. Nature 356, 721–722 (1992)Describes first causative mutation to be identified in a familial form of diabetes.

    Google Scholar 

  14. Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-4α gene in maturity-onset diabetes of the young (MODY1). Nature 384, 458–460 (1996)

    Google Scholar 

  15. Yamagata, K. et al. Mutations in the hepatocyte nuclear factor-1α gene in maturity-onset diabetes of the young (MODY3). Nature 384, 455–458 (1996)Refs 14 and 15 highlight the importance of mutations in the HNF family of transcription factors in the causation of familial forms of diabetes.

    Google Scholar 

  16. Stoffers, D. A., Ferrer, J., Clarke, W. L. & Habener, J. F. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1 . Nature Genet. 17, 138–139 (1997)

    Google Scholar 

  17. Horikawa, Y. et al. Mutation in hepatocyte nuclear factor-1 β gene (TCF2) associated with MODY. Nature Genet. 17, 384–385 (1997)

    Google Scholar 

  18. Malecki, M. T. et al. Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus. Nature Genet. 23, 323–328 (1999)

    Google Scholar 

  19. Babenko, A. P. et al. Activating mutations in the ABCC8 gene in neonatal diabetes mellitus. N. Engl. J. Med. 355, 456–466 (2006)

    Google Scholar 

  20. Gloyn, A. L. et al. Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes. N. Engl. J. Med. 350, 1838–1849 (2004); erratum 351, 1470 (2004)Refs 19 and 20 demonstrate that mutations constitutively activating the voltage-gated potassium channel in the pancreatic beta cell could lead to insulin-deficient diabetes from birth.

    Google Scholar 

  21. Støy, J. et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc. Natl Acad. Sci. USA 104, 15040–15044 (2007)

    Google Scholar 

  22. Gill-Carey, O. & Hattersley, A. T. Genetics and type 2 diabetes in youth. Pediatr. Diabetes 8 (Suppl. 9). 42–47 (2007)

    Google Scholar 

  23. Yoshimasa, Y. et al. Insulin-resistant diabetes due to a point mutation that prevents insulin proreceptor processing. Science 240, 784–787 (1988)

    Google Scholar 

  24. Accili, D. et al. Insulin resistance due to mutations of the insulin receptor gene: an overview. J. Endocrinol. Invest. 11, 857–864 (1992)

    Google Scholar 

  25. George, S. et al. A family with severe insulin resistance and diabetes due to a mutation in AKT2 . Science 304, 1325–1328 (2004)

    Google Scholar 

  26. Dash, S. et al. A truncation mutation in TBC1D4 in a family with acanthosis nigricans and postprandial hyperinsulinemia. Proc. Natl Acad. Sci. USA 106, 9350–9355 (2009)

    Google Scholar 

  27. McGarry, J. D. What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258, 766–770 (1992)A highly influential commentary that helped switch attention from glucose to lipid metabolism in type 2 diabetes.

    Google Scholar 

  28. Barroso, I. et al. Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402, 880–883 (1999)The first evidence in any species that disruption of PPARγ function has a severe impact on insulin sensitivity.

    Google Scholar 

  29. Shackleton, S. et al. LMNA, encoding lamin A/C, is mutated in partial lipodystrophy. Nature Genet. 24, 153–156 (2000)

    Google Scholar 

  30. Magré, J. et al. Identification of the gene altered in Berardinelli-Seip congenital lipodystrophy on chromosome 11q13. Nature Genet. 28, 365–370 (2001)

    Google Scholar 

  31. Agarwal, A. K. et al. AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34. Nature Genet. 31, 21–23 (2002)

    Google Scholar 

  32. Kim, C. A. et al. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy. J. Clin. Endocrinol. Metab. 93, 1129–1134 (2008)

    Google Scholar 

  33. Rubio-Cabezas, O. et al. Partial lipodystrophy and insulin resistant diabetes in a patient with a homozygous nonsense mutation in CIDEC . EMBO Mol. Med 1, 280–287 (2009)

    Google Scholar 

  34. McCarthy, M. I. & Zeggini, E. Genome-wide association studies in type 2 diabetes. Curr. Diab. Rep. 9, 164–171 (2009)

    Google Scholar 

  35. Stancáková, A. et al. Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 non-diabetic Finnish Men. Diabetes 58, 2129–2136 (2009)

    Google Scholar 

  36. Pascoe, L. et al. Common variants of the novel type 2 diabetes genes CDKAL1 and HHEX/IDE are associated with decreased pancreatic beta-cell function. Diabetes 56, 3101–3104 (2007)

    Google Scholar 

  37. Grarup, N. et al. Studies of association of variants near the HHEX, CDKN2A/B, and IGF2BP2 genes with type 2 diabetes and impaired insulin release in 10,705 Danish subjects: validation and extension of genome-wide association studies. Diabetes 56, 3105–3111 (2007)

    Google Scholar 

  38. Palmer, N. D. et al. Association of TCF7L2 gene polymorphisms with reduced acute insulin response in Hispanic Americans. J. Clin. Endocrinol. Metab. 93, 304–309 (2008)

    Google Scholar 

  39. Palmer, N. D. et al. Quantitative trait analysis of type 2 diabetes susceptibility loci identified from whole genome association studies in the Insulin Resistance Atherosclerosis Family Study. Diabetes 57, 1093–1100 (2008)

    Google Scholar 

  40. Bouatia-Naji, N. et al. A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. Science 320, 1085–1088 (2008)

    Google Scholar 

  41. Bouatia-Naji, N. et al. A variant near MTNR1B is associated with increased fasting plasma glucose levels and type 2 diabetes risk. Nature Genet. 41, 89–94 (2009)

    Google Scholar 

  42. Prokopenko, I. et al. Variants in MTNR1B influence fasting glucose levels. Nature Genet. 41, 77–81 (2009)

    Google Scholar 

  43. Porte, D. & Kahn, S. E. The key role of islet dysfunction in type II diabetes mellitus. Clin. Invest. Med. 18, 247–254 (1995)

    Google Scholar 

  44. Tuomilehto, J. et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N. Engl. J. Med. 344, 1343–1350 (2001)

    Google Scholar 

  45. Reaven, G. M. The fourth musketeer—from Alexandre Dumas to Claude Bernard. Diabetologia 38, 3–13 (1995)

    Google Scholar 

  46. Højlund, K., Mogensen, M., Sahlin, K. & Beck-Nielsen, H. Mitochondrial dysfunction in type 2 diabetes and obesity. Endocrinol. Metab. Clin. North Am. 37, 713–731 (2008)

    Google Scholar 

  47. Harding, H. P. & Ron, D. Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes 51 (Suppl. 3). S455–S461 (2002)

    Google Scholar 

  48. Shoelson, S. E., Lee, J. & Goldfine, A. B. Inflammation and insulin resistance. J. Clin. Invest. 116, 1793–1801 (2006)

    Google Scholar 

  49. van den Ouweland, J. M. et al. Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nature Genet. 1, 368–371 (1992)

    Google Scholar 

  50. Inoue, H. et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nature Genet. 20, 143–148 (1998)

    Google Scholar 

  51. Sandhu, M. S. et al. Common variants in WFS1 confer risk of type 2 diabetes. Nature Genet. 39, 951–953 (2007)

    Google Scholar 

  52. Fonseca, S. G. et al. WFS1 is a novel component of the unfolded protein response and maintains homeostasis of the endoplasmic reticulum in pancreatic beta-cells. J. Biol. Chem. 280, 39609–39615 (2005)

    Google Scholar 

  53. Delépine, M. et al. EIF2AK3, encoding translation initiation factor 2-α kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nature Genet. 25, 406–409 (2000)

    Google Scholar 

  54. Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007)

  55. Meigs, J. B. et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N. Engl. J. Med. 359, 2208–2219 (2008)

    Google Scholar 

  56. Lyssenko, V. et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N. Engl. J. Med. 359, 2220–2232 (2008)

    Google Scholar 

  57. Hattersley, A. T. & Pearson, E. R. Minireview: pharmacogenetics and beyond: the interaction of therapeutic response, beta-cell physiology, and genetics in diabetes. Endocrinology 147, 2657–2663 (2006)

    Google Scholar 

  58. Kopelman, P. G. Obesity as a medical problem. Nature 404, 635–643 (2000)

    Google Scholar 

  59. Jéquier, E. Energy expenditure in obesity. Clin. Endocrinol. Metab. 13, 563–580 (1984)

    Google Scholar 

  60. Lissner, L. Measuring food intake in studies of obesity. Public Health Nutr. 5, 889–892 (2002)

    Google Scholar 

  61. Montague, C. T. et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387, 903–908 (1997)

    Google Scholar 

  62. Jackson, R. S. et al. Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nature Genet. 16, 303–306 (1997)Refs 61 and 62 describe the first two genetic defects found to cause familial forms of human obesity.

    Google Scholar 

  63. Zhang, Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 372, 425–432 (1994)Paper describing the discovery of leptin as an adipocyte-derived hormone with a role in the control of energy balance.

    Article  Google Scholar 

  64. Huszar, D. et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 88, 131–141 (1997)First definitive evidence for the role of melanocortin 4 receptor in the control of body weight.

    Google Scholar 

  65. O’Rahilly, S. & Farooqi, I. S. Human obesity: a heritable neurobehavioral disorder that is highly sensitive to environmental conditions. Diabetes 57, 2905–2910 (2008)

    Google Scholar 

  66. Krakoff, J. et al. Lower metabolic rate in individuals heterozygous for either a frameshift or a functional missense MC4R variant. Diabetes 57, 3267–3272 (2008)

    Google Scholar 

  67. Nogueiras, R. et al. The central melanocortin system directly controls peripheral lipid metabolism. J. Clin. Invest. 117, 3475–3488 (2007)

    Google Scholar 

  68. Badano, J. L., Mitsuma, N., Beales, P. L. & Katsanis, N. The ciliopathies: an emerging class of human genetic disorders. Annu. Rev. Genomics Hum. Genet. 7, 125–148 (2006)

    Google Scholar 

  69. Frayling, T. M. et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316, 889–894 (2007)First description of a common human obesity gene discovered through a genome-wide association approach.

    Google Scholar 

  70. Dina, C. et al. Variation in FTO contributes to childhood obesity and severe adult obesity. Nature Genet. 39, 724–726 (2007)

    Google Scholar 

  71. Gerken, T. et al. The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318, 1469–1472 (2007)

    Google Scholar 

  72. Cecil, J. E. et al. An obesity-associated FTO gene variant and increased energy intake in children. N. Engl. J. Med. 359, 2558–2566 (2008)

    Google Scholar 

  73. Fischer, J. et al. Inactivation of the Fto gene protects from obesity. Nature 458, 894–898 (2009)

    Google Scholar 

  74. Loos, R. J. et al. Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nature Genet. 40, 768–775 (2008)This study reports a common variant in the vicinity of MC4R associated with human obesity.

    Google Scholar 

  75. Qi, L., Kraft, P., Hunter, D. J. & Hu, F. B. The common obesity variant near MC4R gene is associated with higher intakes of total energy and dietary fat, weight change and diabetes risk in women. Hum. Mol. Genet. 17, 3502–3508 (2008)

    Google Scholar 

  76. Willer, C. J. et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genet. 41, 25–34 (2009)

    Google Scholar 

  77. Rung, J. et al. Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Nature Genet. 41, 1110–1115 (2009)

    Google Scholar 

  78. Lindgren, C. M. et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet. 5, e1000508 (2009)

    Google Scholar 

  79. Temple, I. K. et al. An imprinted gene(s) for diabetes? Nature Genet. 9, 110–112 (1995)

    Google Scholar 

  80. Mackay, D. J. et al. Hypomethylation of multiple imprinted loci in individuals with transient neonatal diabetes is associated with mutations in ZFP57 . Nature Genet. 40, 949–951 (2008)

    Google Scholar 

  81. Ræder, H. et al. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction. Nature Genet. 38, 54–62 (2006)

    Google Scholar 

  82. Hearn, T. et al. Mutation of ALMS1, a large gene with a tandem repeat encoding 47 amino acids, causes Alström syndrome. Nature Genet. 31, 79–83 (2002)

    Google Scholar 

  83. Collin, G. B. et al. Mutations in ALMS1 cause obesity, type 2 diabetes and neurosensory degeneration in Alström syndrome. Nature Genet. 31, 74–78 (2002)

    Google Scholar 

  84. McCarthy, M. I. & Hattersley, A. T. Learning from molecular genetics: novel insights arising from the definition of genes for monogenic and type 2 diabetes. Diabetes 57, 2889–2898 (2008)

    Google Scholar 

  85. Zeggini, E. et al. Meta analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type-2 diabetes. Nature Genet. 40, 638–645 (2008)

    Google Scholar 

  86. Deeb, S. S. et al. A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nature Genet. 20, 284–287 (1998)The first association between a common SNP in PPARγ and type 2 diabetes.

    Google Scholar 

  87. Saxena, R. et al. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316, 1331–1336 (2007)

    Google Scholar 

  88. Zeggini, E. et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science 316, 1336–1341 (2007)

    Google Scholar 

  89. Scott, L. et al. A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316, 1341–1345 (2007)

    Google Scholar 

  90. Steinthorsdottir, V. et al. A variant in CDKAL1 influences insulin response and risk of type 2 diabetes. Nature Genet. 39, 770–775 (2007)

    Google Scholar 

  91. Sladek, R. et al. A genome-wide association study identifies novel risk loci for type 2 diabetes. Nature 445, 881–885 (2007)The first genome-wide association study in type 2 diabetes, focusing on more severe and early onset cases; identified SNPs are close to several islet genes.

    Google Scholar 

  92. Grant, S. F. et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genet. 38, 320–323 (2006)The first and, so far, most significant common type 2 diabetes gene identified initially through linkage and positional candidate screening in a large Icelandic population.

    Google Scholar 

  93. Florez, J. C. Haplotype structure and genotype-phenotype correlations of the sulphonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes 53, 1360–1368 (2004)

    Google Scholar 

  94. Gudmundsson, J. et al. Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes. Nature Genet. 39, 977–983 (2007)

    Google Scholar 

  95. Clément, K. et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392, 398–401 (1998)

    Google Scholar 

  96. Krude, H. et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nature Genet. 19, 155–157 (1998)

    Google Scholar 

  97. Vaisse, C., Clement, K., Guy-Grand, B. & Froguel, P. A frameshift mutation in human MC4R is associated with a dominant form of obesity. Nature Genet. 20, 113–114 (1998)

    Google Scholar 

  98. Yeo, G. S. et al. A frameshift mutation in MC4R associated with dominantly inherited human obesity. Nature Genet. 20, 111–112 (1998)Refs 97 and 98 are the first descriptions of human melanocortin 4 receptor deficiency, the commonest single gene disorder causing obesity in humans.

    Google Scholar 

  99. Holder, J. L., Butte, N. F. & Zinn, A. R. Profound obesity associated with a balanced translocation that disrupts the SIM1 gene. Hum. Mol. Genet. 9, 101–108 (2000)

    Google Scholar 

  100. Sahoo, T. et al. Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C/D box small nucleolar RNA cluster. Nature Genet. 40, 719–721 (2008)

    Google Scholar 

  101. Spiegel, A. Albright’s hereditary osteodystrophy and defective G proteins. N. Engl. J. Med. 322, 1461–1462 (1990)

    Google Scholar 

  102. Gray, J. et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes 55, 3366–3371 (2006)

    Google Scholar 

  103. Han, J. C. et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. N. Engl. J. Med. 359, 918–927 (2008); erratum 359, 1414 (2008)

    Google Scholar 

  104. Yeo, G. S. et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nature Neurosci. 7, 1187–1189 (2004)

    Google Scholar 

  105. Beales, P. R., Farooqi, I. S. & O’Rahilly, S. (eds) Genetics of Obesity Syndromes (Oxford Univ. Press, 2009)

    Google Scholar 

  106. Thorleifsson, G. et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nature Genet. 41, 18–24 (2009)

    Google Scholar 

  107. Benzinou, M. et al. Common nonsynonymous variants in PCSK1 confer risk of obesity. Nature Genet. 40, 943–945 (2008)

    Google Scholar 

  108. Meyre, D. et al. Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nature Genet. 41, 157–159 (2009)

    Google Scholar 

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Acknowledgements

I thank M. Adams for assistance with this manuscript. I also thank A. Hattersley for many helpful suggestions, and I. Barroso, T. Coll, S. Farooqi, R. Loos, J. Rochford, D. Savage, R. Semple, N. Wareham and G. Yeo for discussions over many years. I acknowledge the support of the MRC Centre for Obesity and Related Metabolic Diseases, the Wellcome Trust, the NIHR Cambridge Biomedical Research Centre, and the EU for their continuing support of our work in this area.

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    Stephen O’Rahilly

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Correspondence to Stephen O’Rahilly.

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[Competing Interests: S.O.R. receives remuneration for scientific advice regarding drug discovery and development from GSK, Pfizer and OSI Pharmaceuticals.]

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O’Rahilly, S. Human genetics illuminates the paths to metabolic disease. Nature 462, 307–314 (2009). https://doi.org/10.1038/nature08532

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