title: Genetics of type 2 diabetes.
abstract: Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this "missing heritability", including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.
authors: Omar Ali, Medical College of Wisconsin, Milwaukee, WI 53226, United States.
authors: Omar
authors: O
authors: Ali
keywords: Genetics; Genome-wide association studies; Heritability; TCF7L2; Type 2 diabetes
references: Nat Genet. 2012 May 13;44(6):659-69
references: 22581228
references: Clin Genet. 2013 Apr;83(4):297-306
references: 23167659
references: Cell. 2012 Dec 21;151(7):1595-607
references: 23260145
references: BMJ. 2010 Jan 14;340:b4838
references: 20075150
references: Curr Diab Rep. 2009 Apr;9(2):164-71
references: 19323962
references: Diabetologia. 1992 Nov;35(11):1060-7
references: 1473616
references: Diabetes. 2008 Nov;57(11):3136-44
references: 18678618
references: Acta Pharmacol Sin. 2010 Jun;31(6):709-17
references: 20523342
references: Diabetologia. 2011 Nov;54(11):2811-9
references: 21826484
references: Genet Mol Res. 2012 May 24;11(2):1592-8
references: 22653633
references: Nat Genet. 2007 Aug;39(8):951-3
references: 17603484
references: Best Pract Res Clin Endocrinol Metab. 2012 Apr;26(2):171-87
references: 22498247
references: Diabetes. 2007 Oct;56(10):2631-7
references: 17579206
references: Metabolism. 2011 May;60(5):681-8
references: 20667559
references: Diabetes. 2003 Feb;52(2):573-7
references: 12540638
references: Diabetes. 2000 Dec;49(12):2201-7
references: 11118026
references: Nutr Metab Cardiovasc Dis. 2012 Nov;22(11):929-36
references: 22819342
references: Mutagenesis. 2013 Jan;28(1):25-37
references: 23188737
references: Diabetologia. 2008 Jul;51(7):1100-10
references: 18504548
references: Epigenetics. 2011 Jul;6(7):838-42
references: 21637037
references: J Clin Endocrinol Metab. 2012 Jul;97(7):E1338-41
references: 22535968
references: Gene. 2013 Jan 25;513(2):244-8
references: 23142382
references: Diabetes. 2008 Jul;57(7):1992-6
references: 18430866
references: Diabetes. 2006 Sep;55(9):2649-53
references: 16936217
references: Diabetologia. 2003 Apr;46(4):567-73
references: 12669197
references: Endocrinology. 2012 Mar;153(3):1025-30
references: 22253427
references: Ann N Y Acad Sci. 2006 Nov;1084:1-29
references: 17151290
references: Breast Cancer Res Treat. 2012 Nov;136(2):593-602
references: 23085767
references: Diabetes. 2002 Dec;51 Suppl 3:S304-7
references: 12475767
references: Diabetes Res Clin Pract. 2012 Dec;98(3):e23-7
references: 23107111
references: Diabetes. 2012 Nov;61(11):2807-13
references: 23086040
references: Int J Obes Relat Metab Disord. 2000 Mar;24(3):391-3
references: 10757637
references: Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):455-9
references: 19536736
references: Diabetes. 2005 Oct;54(10):3035-9
references: 16186411
references: Diabetologia. 1999 Feb;42(2):139-45
references: 10064092
references: Acta Diabetol. 2013 Oct;50(5):657-62
references: 22623142
references: BMC Cancer. 2006 Nov 17;6:268
references: 17109766
references: Exp Clin Endocrinol Diabetes. 2012 Jan;120(1):1-6
references: 21915815
references: Diabetologia. 2007 Dec;50(12):2443-50
references: 17661009
references: Annu Rev Genomics Hum Genet. 2003;4:257-91
references: 14527304
references: Endocr Rev. 2008 May;29(3):254-64
references: 18436708
references: Diabetologia. 2007 Jan;50(1):63-7
references: 17093941
references: Clin Chim Acta. 2010 Aug 5;411(15-16):1126-31
references: 20406624
references: Biochem Biophys Res Commun. 1999 Jan 19;254(2):450-3
references: 9918859
references: Curr Atheroscler Rep. 2011 Jun;13(3):193-201
references: 21487702
references: Diabetes. 2011 Oct;60(10):2624-34
references: 21873549
references: J Clin Invest. 2007 Aug;117(8):2155-63
references: 17671651
references: Nat Genet. 1996 Jun;13(2):161-6
references: 8640221
references: Am J Hum Genet. 1999 Apr;64(4):1127-40
references: 10090898
references: Br J Nurs. 2003 Oct 9-22;12(18):1091-5
references: 14581842
references: PLoS One. 2012;7(11):e49917
references: 23166797
references: Curr Diab Rep. 2011 Dec;11(6):552-61
references: 21887612
references: PLoS Genet. 2012;8(11):e1003041
references: 23166511
references: Nat Genet. 2006 Mar;38(3):320-3
references: 16415884
references: Autoimmunity. 2011 Dec;44(8):616-23
references: 21604969
references: Diabetologia. 1998 Dec;41(12):1511-5
references: 9867219
references: J Endocrinol. 2012 Aug;214(2):225-32
references: 22582094
references: Diabetes. 2012 Nov;61(11):2657-8
references: 23093653
references: Diabetes. 2003 Feb;52(2):568-72
references: 12540637
references: Pediatrics. 2012 Nov;130(5):e1235-42
references: 23071215
references: Diabetes. 2007 Dec;56(12):3105-11
references: 17827400
references: Lancet. 1995 Aug 12;346(8972):397-402
references: 7623569
references: Nat Genet. 2010 Jul;42(7):579-89
references: 20581827
references: PLoS One. 2012;7(4):e35410
references: 22558147
references: Diabetologia. 2011 Jan;54(1):103-10
references: 20957343
references: J Assoc Physicians India. 2011 Apr;59 Suppl:6-7
references: 21818991
references: Diabetes. 2007 Oct;56(10):2638-42
references: 17601994
references: Genetics. 2011 Feb;187(2):367-83
references: 21115973
references: Nature. 2007 Jun 7;447(7145):661-78
references: 17554300
references: Curr Opin Clin Nutr Metab Care. 2007 Jul;10(4):420-6
references: 17563459
references: Am J Hum Genet. 2004 Feb;74(2):208-22
references: 14730479
references: J Clin Endocrinol Metab. 2002 Aug;87(8):3859-63
references: 12161522
references: Nature. 2007 Feb 22;445(7130):881-5
references: 17293876
references: Nat Rev Genet. 2012 Jan 18;13(2):135-45
references: 22251874
references: Endocrinology. 2012 Mar;153(3):1031-8
references: 22253432
references: Ann N Y Acad Sci. 2010 Nov;1212:59-77
references: 21091714
references: Diabetes Metab. 2010 Nov;36(5):357-62
references: 20570542
references: Diabetes. 2004 May;53(5):1360-8
references: 15111507
references: PLoS One. 2012;7(3):e33140
references: 22427968
references: J Hum Genet. 2008;53(2):174-180
references: 18097733
references: Diabetes. 1987 Jan;36(1):93-9
references: 3792666
references: BMC Med Genet. 2009 Feb 19;10:15
references: 19228405
references: Diabetologia. 2008 Mar;51(3):458-63
references: 18040659
references: Nat Genet. 2000 Oct;26(2):163-75
references: 11017071