Recent advances in understanding the genetic architecture of type 2 diabetes

Human Molecular Genetics

Volumn 24, Issue R1, 2015, Pages R85-R92

  Mohlke, Karen L ^a   Boehnke, Michael ^b  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MICHIGAN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GLUCOSE; HEMOGLOBIN A1C; INSULIN; PROINSULIN; GLUCOSE BLOOD LEVEL;

BODY MASS; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE LOCUS; GENETIC ASSOCIATION; GENETIC TRAIT; GENETIC VARIABILITY; GENOTYPE; HIGH THROUGHPUT SEQUENCING; HUMAN; INSULIN RESISTANCE; META ANALYSIS (TOPIC); NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; REVIEW; SAMPLE SIZE; BLOOD; GENETIC VARIATION; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GLUCOSE BLOOD LEVEL; METABOLISM; SINGLE NUCLEOTIDE POLYMORPHISM;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; GENE FREQUENCY; GENETIC VARIATION; GENOME-WIDE ASSOCIATION STUDY; HUMANS; POLYMORPHISM, SINGLE NUCLEOTIDE;

EID: 84943785470     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddv264     Document Type: Review

References (60)

1. Danaei, G., Finucane, M.M., Lu, Y., Singh, G.M., Cowan, M.J., Paciorek, C.J., Lin, J.K., Farzadfar, F., Khang, Y.H., Stevens, G. A. et al. (2011) National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet, 378, 31-40.
2. International Expert Committee. (2009) International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care, 32, 1327-1334.
3. NCEP Expert Panel. (2002) Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation, 106, 3143-3421.
4. Fonseca, V.A. (2009) Defining and characterizing the progression of type 2 diabetes. Diabetes Care, 32 Suppl 2, S151-S156.
5. Poulsen, P., Kyvik, K.O., Vaag, A. Beck-Nielsen, H. (1999) Heritability of type II (non-insulin-dependent) diabetes mellitus and abnormal glucose tolerance-a population-based twin study. Diabetologia, 42, 139-145.
6. Poulsen, P., Levin, K., Petersen, I., Christensen, K., Beck-Nielsen, H. Vaag, A. (2005) Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins. Diabetes, 54, 275-283.
7. Schwitzgebel, V.M. (2014) Many faces of monogenic diabetes. Diabetes Invest., 5, 121-133.
8. Vaxillaire, M., Bonnefond, A. Froguel, P. (2012) The lessons of early-onsetmonogenic diabetes for the understanding of diabetes pathogenesis. Best Pract. Res. Clin. Endocrinol. Metab., 26, 171-187.
9. Agarwala, V., Flannick, J., Sunyaev, S., GoT2D Consortium and Altshuler, D. (2013) Evaluating empirical bounds on complex disease genetic architecture. Nat. Genet., 45, 1418-1427.
10. Mohlke, K.L., Boehnke, M. Abecasis, G.R. (2008) Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants. Hum. Mol. Genet., 17, R102-R108.
11. Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., Ng, D.P., Holmkvist, J., Borch-Johnsen, K., Jorgensen, T. et al. (2008) SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations. Nat. Genet., 40, 1098-1102.
12. Yasuda, K., Miyake, K., Horikawa, Y., Hara, K., Osawa, H., Furuta, H., Hirota, Y., Mori, H., Jonsson, A., Sato, Y. et al. (2008) Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus. Nat. Genet., 40, 1092-1097.
13. McCarthy, M.I. (2008) Casting a wider net for diabetes susceptibility genes. Nat. Genet., 40, 1039-1040.
14. Voight, B.F., Scott, L.J., Steinthorsdottir, V., Morris, A.P., Dina, C., Welch, R.P., Zeggini, E., Huth, C., Aulchenko, Y.S., Thorleifsson, G. et al. (2010) Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat. Genet., 42, 579-589.
15. Visscher, P.M., Brown, M.A., McCarthy, M.I. Yang, J. (2012) Five years of GWAS discovery. Am. J. Hum. Genet., 90, 7-24.
16. Cho, Y.S., Chen, C.H., Hu, C., Long, J., Ong, R.T., Sim, X., Takeuchi, F., Wu, Y., Go, M.J., Yamauchi, T. et al. (2012) Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians. Nat. Genet., 44, 67-72.
17. Kim, Y.J., Go, M.J., Hu, C., Hong, C.B., Kim, Y.K., Lee, J.Y., Hwang, J.Y., Oh, J.H., Kim, D.J., Kim, N.H. et al. (2011) Largescale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. Nat. Genet., 43, 990-995.
18. Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A.U., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Gloyn, A.L. et al. (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet., 42, 105-116.
19. Saxena, R., Hivert, M.F., Langenberg, C., Tanaka, T., Pankow, J. S., Vollenweider, P., Lyssenko, V., Bouatia-Naji, N., Dupuis, J., Jackson, A.U. et al. (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat. Genet., 42, 142-148.
20. Pare, G., Chasman, D.I., Parker, A.N., Nathan, D.M., Miletich, J. P., Zee, R.Y. Ridker, P.M. (2008) Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14, 618 participants in the Women's Genome Health Study. PLoS Genet., 4, e1000312.
21. Soranzo, N., Sanna, S., Wheeler, E., Gieger, C., Radke, D., Dupuis, J., Bouatia-Naji, N., Langenberg, C., Prokopenko, I., Stolerman, E. et al. (2010) Common variants at ten genomic loci influence hemoglobin A1C levels via glycemic and non-glycemic pathways. Diabetes, 59, 3229-3239.
22. Kamatani, Y., Matsuda, K., Okada, Y., Kubo, M., Hosono, N., Daigo, Y., Nakamura, Y. Kamatani, N. (2010) Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat. Genet., 42, 210-215.
23. Strawbridge, R.J., Dupuis, J., Prokopenko, I., Barker, A., Ahlqvist, E., Rybin, D., Petrie, J.R., Travers, M.E., Bouatia-Naji, N., Dimas, A.S. et al. (2011) Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. Diabetes, 60, 2624-2634.
24. Voight, B.F., Kang, H.M., Ding, J., Palmer, C.D., Sidore, C., Chines, P.S., Burtt, N.P., Fuchsberger, C., Li, Y., Erdmann, J. et al. (2012) The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. PLoS Genet., 8, e1002793.
25. Morris, A.P., Voight, B.F., Teslovich, T.M., Ferreira, T., Segre, A. V., Steinthorsdottir, V., Strawbridge, R.J., Khan, H., Grallert, H., Mahajan, A. et al. (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat. Genet., 44, 981-990.
26. Saxena, R., Elbers, C.C., Guo, Y., Peter, I., Gaunt, T.R., Mega, J.L., Lanktree, M.B., Tare, A., Castillo, B.A., Li, Y.R. et al. (2012) Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. Am. J. Hum. Genet., 90, 410-425.
27. Scott, R.A., Lagou, V., Welch, R.P., Wheeler, E., Montasser, M. E., Luan, J., Magi, R., Strawbridge, R.J., Rehnberg, E., Gustafsson, S. et al. (2012) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat. Genet., 44, 991-1005.
28. Palmer, N.D., McDonough, C.W., Hicks, P.J., Roh, B.H., Wing, M.R., An, S.S., Hester, J.M., Cooke, J.N., Bostrom, M.A., Rudock, M.E. et al. (2012) A genome-wide association search for type 2 diabetes genes in African Americans. PLoS ONE, 7, e29202.
29. Ng, M.C., Shriner, D., Chen, B.H., Li, J., Chen, W.M., Guo, X., Liu, J., Bielinski, S.J., Yanek, L.R., Nalls, M.A. et al. (2014) Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet., 10, e1004517.
30. Tabassum, R., Chauhan, G., Dwivedi, O.P., Mahajan, A., Jaiswal, A., Kaur, I., Bandesh, K., Singh, T., Mathai, B.J., Pandey, Y. et al. (2013) Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21. Diabetes, 62, 977-986.
31. Saxena, R., Saleheen, D., Been, L.F., Garavito, M.L., Braun, T., Bjonnes, A., Young, R., Ho, W.K., Rasheed, A., Frossard, P. et al. (2013) Genome-wide association study identifies novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India. Diabetes, 62, 1746-1755.
32. Hara, K., Fujita, H., Johnson, T.A., Yamauchi, T., Yasuda, K., Horikoshi, M., Peng, C., Hu, C., Ma, R.C., Imamura, M. et al. (2014) Genome-wide association study identifies three novel loci for type 2 diabetes. Hum. Mol. Genet., 23, 239-246.
33. SIGMAType 2 Diabetes Consortium. (2014) Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. Nature, 506, 97-101.
34. Imamura, M., Maeda, S., Yamauchi, T., Hara, K., Yasuda, K., Morizono, T., Takahashi, A., Horikoshi, M., Nakamura, M., Fujita, H. et al. (2012) A single-nucleotide polymorphism in ANK1 is associated with susceptibility to type 2 diabetes in Japanese populations. Hum. Mol. Genet., 21, 3042-3049.
35. Li, H., Gan, W., Lu, L., Dong, X., Han, X., Hu, C., Yang, Z., Sun, L., Bao, W., Li, P. et al. (2013) A genome-wide association study identifies GRK5 and RASGRP1 as type 2 diabetes loci in Chinese Hans. Diabetes, 62, 291-298.
36. Go, M.J., Hwang, J.Y., Park, T.J., Kim, Y.J., Oh, J.H., Kim, Y.J., Han, B.G. Kim, B.J. (2014) Genome-wide association study identifies two novel loci with sex-specific effects for type 2 diabetes mellitus and glycemic traits in a Korean population. Diabetes Metab. J., 38, 375-387.
37. Moltke, I., Grarup, N., Jorgensen, M.E., Bjerregaard, P., Treebak, J.T., Fumagalli, M., Korneliussen, T.S., Andersen, M.A., Nielsen, T.S., Krarup, N.T. et al. (2014) A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes. Nature, 512, 190-193.
38. Albrechtsen, A., Grarup, N., Li, Y., Sparso, T., Tian, G., Cao, H., Jiang, T., Kim, S.Y., Korneliussen, T., Li, Q. et al. (2013) Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Diabetologia, 56, 298-310.
39. Hanson, R.L., Muller, Y.L., Kobes, S., Guo, T., Bian, L., Ossowski, V., Wiedrich, K., Sutherland, J., Wiedrich, C., Mahkee, D. et al. (2014) A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes. Diabetes, 63, 369-376.
40. 1000 Genomes Project Consortium. (2012) An integrated map of genetic variation from 1092 human genomes. Nature, 491, 56-65.
41. Chen, G., Bentley, A., Adeyemo, A., Shriner, D., Zhou, J., Doumatey, A., Huang, H., Ramos, E., Erdos, M., Gerry, N. et al. (2012) Genome-wide association study identifies novel loci association with fasting insulin and insulin resistance in African Americans. Hum. Mol. Genet., 21, 4530-4536.
42. Go, M.J., Hwang, J.Y., Kim, Y.J., Hee Oh, J., Kim, Y.J., Heon Kwak, S., Soo Park, K., Lee, J., Kim, B.J., Han, B.G. et al. (2013) New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population. J. Hum. Genet., 58, 362-365.
43. Hwang, J.Y., Sim, X., Wu, Y., Liang, J., Tabara, Y., Hu, C., Hara, K., Tam, C.H., Cai, Q., Zhao, Q. et al. (2015) Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. Diabetes, 64, 291-298.
44. Chen, P., Takeuchi, F., Lee, J.Y., Li, H., Wu, J.Y., Liang, J., Long, J., Tabara, Y., Goodarzi, M.O., Pereira, M.A. et al. (2014) Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians. Diabetes, 63, 2551-2562.
45. Huyghe, J.R., Jackson, A.U., Fogarty, M.P., Buchkovich, M.L., Stancakova, A., Stringham, H.M., Sim, X., Yang, L., Fuchsberger, C., Cederberg, H. et al. (2013) Exome array analysis identifies new loci and low-frequency variants influencing insulin processing and secretion. Nat. Genet., 45, 197-201.
46. Wessel, J., Chu, A.Y., Willems, S.M., Wang, S., Yaghootkar, H., Brody, J.A., Dauriz, M., Hivert, M.F., Raghavan, S., Lipovich, L. et al. (2015) Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat. Commun., 6, 5897.
47. Dimas, A.S., Lagou, V., Barker, A., Knowles, J.W., Magi, R., Hivert, M.F., Benazzo, A., Rybin, D., Jackson, A.U., Stringham, H. M. et al. (2014) Impact of type 2 diabetes susceptibility variants on quantitative glycemic traits reveals mechanistic heterogeneity. Diabetes, 63, 2158-2171.
48. DIAbetes Genetics Replication Meta-analysis Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGENT2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium and Type 2 Diabetes Genetic Exploration by Next-generation sequencing in multi-Ethnic Samples (T2DGENES) Consortium. (2014) Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet., 46, 234-244.
49. The International HapMap Consortium. (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature, 449, 851-861.
50. Perry, J.R., Voight, B.F., Yengo, L., Amin, N., Dupuis, J., Ganser, M., Grallert, H., Navarro, P., Li, M., Qi, L. et al. (2012) Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases. PLoS Genet., 8, e1002741.
51. Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Prokopenko, I. et al. (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat. Genet., 44, 659-669.
52. Steinthorsdottir, V., Thorleifsson, G., Sulem, P., Helgason, H., Grarup, N., Sigurdsson, A., Helgadottir, H.T., Johannsdottir, H., Magnusson, O.T., Gudjonsson, S.A. et al. (2014) Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat. Genet., 46, 294-298.
53. Mahajan, A., Sim, X., Ng, H.J., Manning, A., Rivas, M.A., Highland, H.M., Locke, A.E., Grarup, N., Im, H.K., Cingolani, P. et al. (2015) Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus. PLoS Genet., 11, e1004876.
54. Flannick, J., Thorleifsson, G., Beer, N.L., Jacobs, S.B., Grarup, N., Burtt, N.P., Mahajan, A., Fuchsberger, C., Atzmon, G., Benediktsson, R. et al. (2014) Loss-of-function mutations in SLC30A8protectagainst type2diabetes. Nat. Genet., 46, 357-363.
55. Sigma Type 2 Diabetes Consortium. (2014) Association of a low-frequency variant in HNF1A with type 2 diabetes in a Latino population. JAMA, 311, 2305-2314.
56. Cornes, B.K., Brody, J.A., Nikpoor, N., Morrison, A.C., Dang, H. C., Ahn, B.S., Wang, S., Dauriz, M., Barzilay, J.I., Dupuis, J. et al. (2014) Association of levels of fasting glucose and insulin with rare variants at the chromosome 11p11.2-MADD locus: Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium Targeted Sequencing Study. Circ. Cardiovasc. Genet., 7, 374-382.
57. Bonnefond, A., Clement, N., Fawcett, K., Yengo, L., Vaillant, E., Guillaume, J.L., Dechaume, A., Payne, F., Roussel, R. Czernichow, S. et al. (2012) Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes. Nat. Genet., 44, 297-301.
58. Majithia, A.R., Flannick, J., Shahinian, P., Guo, M., Bray, M.A., Fontanillas, P., Gabriel, S.B., GoT2D Consortium, NHGRI JHS/FHS Allelic Spectrum Project, SIGMA Type 2 Diabetes Consortium et al. (2014) Rare variants in PPARG with decreased activity in adipocyte differentiation are associated with increased risk of type 2 diabetes. Proc. Natl. Acad. Sci. U. S. A., 111, 13127-13132.
59. Kong, A., Steinthorsdottir, V., Masson, G., Thorleifsson, G., Sulem, P., Besenbacher, S., Jonasdottir, A., Sigurdsson, A., Kristinsson, K.T., Jonasdottir, A. et al. (2009) Parental origin of sequence variants associated with complex diseases. Nature, 462, 868-874.
60. Hanson, R.L., Guo, T., Muller, Y.L., Fleming, J., Knowler, W.C., Kobes, S., Bogardus, C. Baier, L.J. (2013) Strong parent-of-origin effects in the association of KCNQ1 variants with type 2 diabetes in American Indians. Diabetes, 62, 2984-2991.