Advertisement

Heterogeneous impact of type 2 diabetes mellitus-related genetic variants on gestational glycemic traits: review and future research needs

  • Shasha Liu
  • Yunqiang Liu
  • Shunyao LiaoEmail author
Review

Abstract

Gestational glucose homeostasis influences mother’s metabolic health, pregnancy outcomes, fetal development and offspring growth. To understand the genetic roles in pregnant glucose metabolism and genetic predisposition for gestational diabetes (GDM), we reviewed the recent literature up to Jan, 2018 and evaluated the influence of T2DM-related genetic variants on gestational glycemic traits and glucose tolerance. A total of 140 variants of 89 genes were integrated. Their associations with glycemic traits in and outside pregnancy were compared. The genetic circumstances underlying glucose metabolism exhibit a similarity between pregnant and non-pregnant populations. While, not all of the T2DM-associated genetic variants are related to pregnant glucose tolerance, such as genes involved in fasting insulin/C-peptide regulation. Some genetic variants may have distinct effects on gestational glucose homeostasis. And certain genes may be particularly involved in this process via specific mechanisms, such as HKDC1, MTNR1B, BACE2, genes encoding cell cycle regulators, adipocyte regulators, inflammatory factors and hepatic factors related to gestational glucose sensing and insulin signaling. However, it is currently difficult to evaluate these associations with quantitative synthesis due to inadequate data, different analytical methods, varied measurements for glycemic traits, controversies in diagnosis of GDM, and unknown ethnicity- and/or sex-related influences on pregnant maternal metabolism. In conclusion, different genetic associations with glycemic traits may exist between pregnant and non-pregnant conditions. Comprehensive research on specific genetic regulation in gestation is necessary.

Keywords

Genetic association Glucose tolerance Gestational glycemic traits Genetic variants Type 2 diabetes mellitus Gestational diabetes mellitus 

Notes

Acknowledgements

Data on glycemic traits have been contributed by MAGIC investigators and have been downloaded from website of http://www.magicinvestigators.org. Also, data on T2DM have been downloaded by DIAGRAM consortium.

Funding

This study was funded by the National Natural Science Foundation of China (81471430).

Compliance with ethical standards

Conflict of interest

Shasha Liu declares that she has no conflict of interest. Yunqiang Liu declares that he has no conflict of interest. Shunyao Liao declares that she has no conflict of interest.

Ethical statement

This article does not contain any studies with human participants or animals performed by any of the authors.

References

  1. Al-Hakeem MM (2014) Implication of SH2B1 gene polymorphism studies in gestational diabetes mellitus in Saudi pregnant women. Saudi J Biol Sci 21(6):610–615Google Scholar
  2. Al-Hakeem MM, Abotalib Z, Alharbi KK, Khan IA (2014) Relationship between the paraoxonase 1 gene glutamine 192 to arginine polymorphism and gestational diabetes mellitus in Saudi women. Clin Biochem 47(15):122–125Google Scholar
  3. Anghebem-Oliveira MI, Webber S, Alberton D, de Souza EM, Klassen G, Picheth G, Rego FG (2017) The GCKR gene polymorphism rs780094 is a risk factor for gestational diabetes in a Brazilian population. J Clin Lab Anal.  https://doi.org/10.1002/jcla.22035 Google Scholar
  4. Ao D, Wang HJ, Wang LF, Song JY, Yang HX, Wang Y (2015) The rs2237892 polymorphism in KCNQ1 influences gestational diabetes mellitus and glucose levels: a case-control study and meta-analysis. PLoS One 10(6):e0128901Google Scholar
  5. Araújo JR, Keating E, Martel F (2015) Impact of gestational diabetes mellitus in the maternal-to-fetal transport of nutrients. Curr Diab Rep 15(2):569Google Scholar
  6. Beltcheva O, Boyadzhieva M, Angelova O, Mitev V, Kaneva R, Atanasova I (2014) The rs266729 single-nucleotide polymorphism in the adiponectin gene shows association with gestational diabetes. Arch Gynecol Obstet 289(4):743–748Google Scholar
  7. Bradnová O, Vejražková D, Vaňková M, Lukášová P, Včelák J, Stanická S, Dvořáková K, Bendlová B (2015) Metabolic and hormonal consequencies of the “obesity risk” MC4R variant (rs12970134) in Czech women. Physiol Res 64(Suppl 2):S187–S195Google Scholar
  8. Brelje TC, Scharp DW, Lacy PE, Ogren L, Talamantes F, Robertson M, Friesen HG, Sorenson RL (1993) Effect of homologous placental lactogens, prolactins, and growth hormones on islet B-cell division and insulin secretion in rat, mouse, and human islets: implication for placental lactogen regulation of islet function during pregnancy. Endocrinology 132(2):879–887Google Scholar
  9. Buchanan TA, Xiang AH (2005) Gestational diabetes mellitus. J Clin Invest 115(3):485–491Google Scholar
  10. Chen YP, Li J, Wang ZN, Reichetzeder C, Xu H, Gong J, Chen GJ, Pfab T, Xiao XM, Hocher B (2012) Renin angiotensin aldosterone system and glycemia in pregnancy. Clin Lab. 58(5–6):527–533Google Scholar
  11. Chen T, Xu J, Liu G, Liu H, Chen M, Qin Y, Wu W, Xia Y, Ji C, Guo X, Wen J, Wang X (2016) Genetic variants in PTPRD and risk of gestational diabetes mellitus. Oncotarget 7(46):76101–76107Google Scholar
  12. Cho YM, Kim TH, Lim S, Choi SH, Shin HD, Lee HK, Park KS, Jang HC (2009) Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population. Diabetologia 52(2):253–261Google Scholar
  13. Chon SJ, Kim SY, Cho NR, Min DL, Hwang YJ, Mamura M (2013) Association of variants in PPARγ2, IGF2BP2, and KCNQ1 with a susceptibility to gestational diabetes mellitus in a Korean population. Yonsei Med J 54(2):352–357Google Scholar
  14. Dereke J, Palmqvist S, Nilsson C, Landin-Olsson M, Hillman M (2016) The prevalence and predictive value of the SLC30A8 R325 W polymorphism and zinc transporter 8 autoantibodies in the development of GDM and postpartum type 1 diabetes. Endocrine 53(3):740–746Google Scholar
  15. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium; Mexican American Type 2 Diabetes (MAT2D) Consortium; Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Conrortium (2014) Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat Genet 46(3):234–244Google Scholar
  16. Dora JM, Wajner SM, Costa JD, Pinto Ribeiro RV, Leiria LB, Lopes MG, Vitali da Silva A, Crispim D, Maia AL (2014) Type 2 deiodinase Thr92Ala polymorphism is associated with disrupted placental activity but not with dysglycemia or adverse gestational outcomes: a genetic association study. Fertil Steril 101(3):833–839Google Scholar
  17. Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Janckson AU, Wheeler E, Glazer NL, Bouatia-Naji N, Gloyn AL, Lindgren CM, Mägi R, Morris AP, Randall J, Johnson T, Elliott P, Rybin D, Thorleifsson G, Steinthorsdottir V, Henneman P, Grallert H, Dehghan A, Hottenga JJ, Franklin CS, Navarro P, Song K, Goel A, Perry JR, Egan JM, Lajunen T, Grarup N, Sparsø T, Doney A, Voight BF, Stringham HM, Li M, Kanoni S, Shrader P, Cavalcanti-Proença C, Kumari M, Qi L, Timpson NJ, Gieger C, Zabena C, Rocheleau G, Ingelsson E, An P, O’Connell J, Luan J, Elliott A, McCarroll SA, Payne F, Roccasecca RM, Pattou F, Sethupathy P, Ardlie K, Ariyurek Y, Balkau B, Barter P, Beilby JP, Ben-Shlomo Y, Benediktsson R, Bennett AJ, Bergmann S, Bochud M, Boerwinkle E, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Böttcher Y, Brunner E, Bumpstead SJ, Charpentier G, Chen YD, Chines P, Clarke R, Coin LJ, Cooper MN, Cornelis M, Crawford G, Crisponi L, Day IN, de Geus EJ, Delplanque J, Dina C, Erdos MR, Fedson AC, Fischer-Rosinsky A, Forouhi NG, Fox CS, Frants R, Franzosi MG, Galan P, Goodarzi MO, Graessler J, Groves CJ, Grundy S, Gwilliam R, Gyllensten U, Hadjadj S, Hallmans G, Hammond N, Han X, Hartikainen AL, Hassanali N, Hayward C, Heath SC, Hercberg S, Herder C, Hicks AA, Hillman DR, Hingorani AD, Hofman A, Hui J, Hung J, Isomaa B, Johnson PR, Jørgensen T, Jula A, Kaakinen M, Kaprio J, Kesaniemi YA, Kivimaki M, Knight B, Koskinen S, Kovacs P, Kyvik KO, Lathrop GM, Lawlor DA, Le Bacquer O, Lecoeur C, Li Y, Lyssenko V, Mahley R, Mangino M, Manning AK, Martínez-Larrad MT, McAteer JB, McCulloch LJ, McPherson R, Meisinger C, Melzer D, Meyre D, Mitchell BD, Morken MA, Mukherjee S, Naitza S, Narisu N, Neville MJ, Oostra BA, Orrù M, Pakyz R, Palmer CN, Paolisso G, Pattaro C, Pearson D, Peden JF, Pedersen NL, Perola M, Pfeiffer AF, Pichler I, Polasek O, Posthuma D, Potter SC, Pouta A, Province MA, Psaty BM, Rathmann W, Rayner NW, Rice K, Ripatti S, Rivadeneira F, Roden M, Rolandsson O, Sandbaek A, Sandhu M, Sanna S, Sayer AA, Scheet P, Scott LJ, Seedorf U, Sharp SJ, Shields B, Sigurethsson G, Sijbrands EJ, Silveira A, Simpson L, Singleton A, Smith NL, Sovio U, Swift A, Syddall H, Syvänen AC, Tanaka T, Thorand B, Tichet J, Tönjes A, Tuomi T, Uitterlinden AG, van Dijk KW, van Hoek M, Varma D, Visvikis-Siest S, Vitart V, Vogelzangs N, Waeber G, Wagner PJ, Walley A, Walters GB, Ward KL, Watkins H, Weedon MN, Wild SH, Willemsen G, Witteman JC, Yarnell JW, Zeggini E, Zelenika D, Zethelius B, Zhai G, Zhao JH, Zillikens MC, Borecki IB, Loos RJ, Meneton P, Magnusson PK, Nathan DM, Williams GH, Hattersley AT, Silander K, Salomaa V, Smith GD, Bornstein SR, Schwarz P, Spranger J, Karpe F, Shuldiner AR, Cooper C, Dedoussis GV, Serrano-Ríos M, Morris AD, Lind L, Palmer LJ, Hu FB, Franks PW, Ebrahim S, Marmot M, Kao WH, Pankow JS, Sampson MJ, Kuusisto J, Laakso M, Hansen T, Pedersen O, Pramstaller PP, Wichmann HE, Illig T, Rudan I, Wright AF, Stumvoll M, Campbell H, Wilson JF, Bergman RN, Buchanan TA, Collins FS, Mohlke KL, Tuomilehto J, Valle TT, Altshuler D, Rotter JI, Siscovick DS, Penninx BW, Boomsma DI, Deloukas P, Spector TD, Frayling TM, Ferrucci L, Kong A, Thorsteinsdottir U, Stefansson K, van Duijn CM, Aulchenko YS, Cao A, Scuteri A, Schlessinger D, Uda M, Ruokonen A, Jarvelin MR, Waterworth DM, Vollenweider P, Peltonen L, Mooser V, Abecasis GR, Wareham NJ, Sladek R, Froguel P, Watanabe RM, Meigs JB, Groop L, Boehnke M, McCarthy MI, Florez JC, Barroso I, DIAGRAM Consortium; GIANT Consortium; Global BPgen Consortium, Anders Hamsten on behalf of Procardis Consortium; MAGIC investigators (2010) New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet 42(2):105–116Google Scholar
  18. Eriksson B, Lof M, Olausson H, Forsum E (2010) Body fat, insulin resistance, energy expenditure and serum concentrations of leptin, adiponectin and resistin before, during and after pregnancy in healthy Swedish women. Br J Nutr 103(1):50–57Google Scholar
  19. Forsum E, Lof M (2007) Energy metabolism during human pregnancy. Annu Rev Nutr 27:277–292Google Scholar
  20. Freathy RM, Hayes MG, Urbanek M, Lowe LP, Lee H, Ackerman C et al (2010) Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study: common genetic variants in GCK and TCF7L2 are associated with fasting and postchallenge glucose levels in pregnancy and with the new consensus definition of gestational diabetes mellitus from the International Association of Diabetes and Pregnancy Study Groups. Diabetes 59(10):2682–2689Google Scholar
  21. Gesteiro E, Sánchez-Muniz FJ, Ortega-Azorín C, Guillén M, Corella D, Bastida S (2016) Maternal and neonatal FTO rs9939609 polymorphism affect insulin sensitivity markers and lipoprotein profile at birth in appropriate-for-gestational-age term neonates. J Physiol Biochem 72(2):169–181Google Scholar
  22. Greenhill C (2015) DNA methylation affects T2DM risk. Nat Rev Endocrinol 11:505Google Scholar
  23. Guo C, Ludvik AE, Arlotto ME, Hayes MG, Armstrong LL, Scholtens DM, Brown CD, Newgard CB, Becker TC, Layden BT, Lowe WL, Reddy TE (2015) Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1. Nat Commun 6:6069Google Scholar
  24. Hakonarson H, Grant SF (2011) Genome-wide association studies (GWAS): impact on elucidating the aetiology of diabetes. Diabetes Metab Res Rev 27(7):685–696Google Scholar
  25. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, Coustan DR, Hadden DR, McCance DR, Hod M, McIntyre HD, Oats JJ, Persson B, Rogers MS, Sacks DA (2008) Hyperglycemia and adverse pregnancy outcomes. N Engl J Med 358(19):1991–2002Google Scholar
  26. Hayes MG, Urbanek M, Hivert MF, Armstrong LL, Morrison J, Guo C, Lowe LP, Scheftner DA, Pluzhnikov A, Levine DM, McHugh CP, Ackerman CM, Bouchard L, Brisson D, Layden BT, Mirel D, Doheny KF, Leya MV, Lown-Hecht RN, Dyer AR, Metzger BE, Reddy TE, Cox NJ, Lowe WL Jr, HAPO Study Cooperative Research Group (2013) Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. Diabetes 62(9):3282–3291Google Scholar
  27. Heude B, Pelloux V, Forhan A, Bedel JF, Lacorte JM, Clément K, Charles MA, EDEN Mother-Child Cohort Study Group (2011) Association of the Pro12Ala and C1431T variants of PPARgamma and their haplotypes with susceptibiity to gestational diabetes. J Clin Endocrinol Metab 96(10):E1656–E1660Google Scholar
  28. Hivert MF, Scholtens DM, Allard C, Nodzenski M, Bouchard L, Brisson D, Lowe LP, McDowell I, Reddy T, Dastani Z, Richards JB, Hayes MG, Lowe WL Jr (2017) Genetic determinants of adiponectin regulation revealed by pregnancy. Obesity (Silver Spring) 25(5):935–944Google Scholar
  29. Huerta-Chagoya A, Vázquez-Cárdenas P, Moreno-Macías H, Tapia-Maruri L, Rodríguez-Guillén R, López-Vite E, Lowe LP, McDowell I, Reddy T, Dastani Z, Richards JB, Hayes MG, Lowe WL Jr, García-Escalante G, Escobedo-Aguirre F, Parra-Covarrubias A, Cordero-Brieño R, Manzo-Carrillo L, Zacarías-Castillo R, Vargas-García C, Aguilar-Salinas C, Tusié-Luna T (2015) Genetic determinants for gestational diabetes mellitus and related metabolic traits in Mexican women. PLoS One 10(5):e0126408Google Scholar
  30. Huopio H, Cederberg H, Vangipurapu J, Hakkarainen H, Pääkkönen M, Kuulasmaa T, Heinonen S, Laakso M (2013) Association of risk variants for type 2 diabetes and hyperglycemia with gestational diabetes. Eur J Endocrinol 169(3):291–297Google Scholar
  31. Jamalpour S, Zain SM, Mosavat M, Mohamed Z, Omar SZ (2018) A case-control study and meta-analysis confirm glucokinase regulatory gene rs780094 is a riskfactor for gestational diabetes mellitus. Gene 650:34–40Google Scholar
  32. Joseph JJ, EchouffoTcheugui JB, Effoe VS, Hsueh WA, Allison MA, Golden SH (2018) Renin-angiotensin-aldosterone system, glucose metabolism and incident type 2 diabetes mellitus: MESA. J Am Heart Assoc. 7(17):e009890Google Scholar
  33. Ju H, Lin R, Yuan Z, Sun Y, Zeng L, Su Z, Jin L (2017) No association detected between seven common variants in the CDKAL1 gene and gestational glycemic traits. Mol Cell Probes 34:64–67Google Scholar
  34. Kanthimathi S, Liju S, Laasya D, Anjana RM, Mohan V, Radha V (2016) Hexokinase domain containing 1 (HKDC1) gene variants and their association with gestational diabetes mellitus in a South Indian population. Ann Hum Genet 80(4):241–245Google Scholar
  35. Kayemba-Kay’s S, Peters C, Geary MP, Hill NR, Mathews DR, Hindmarsh PC (2013) Maternal hyperinsulinism and glycaemic status in the first trimester of pregnancy are associated with the development of pregnancy-induced hypertension and gestational diabetes. Eur J Endocrinol 168(3):413–418Google Scholar
  36. Khan IA, Jahan P, Hasan Q, Rao P (2014) Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus. J Renin Angiotensin Aldosterone Syst 15(4):566–571Google Scholar
  37. Khan IA, Shaik NA, Pasupuleti N, Chava S, Jahan P, Hasan Q, Rao P (2015) Screening of mitochondrial mutations and insertion-deletion polymorphism in gestational diabetesmellitus in the Asian Indian population. Saudi J Biol Sci 22(3):243–248Google Scholar
  38. Kim J, Zhao K, Jiang P, Lu ZX, Wang J, Murray JC, Xing Y (2012) Transcriptome landscape of the human placenta. BMC Genomics 13:115Google Scholar
  39. Kwak SH, Kim SH, Cho YM, Go MJ, Cho YS, Choi SH, Moon MK, Jung HS, Shin HD, Kang HM, Cho NH, Lee IK, Kim SY, Han BG, Jang HC, Park KS (2012) A genome-wide association study of gestational diabetes mellitus in Korean women. Diabetes 61(2):531–541Google Scholar
  40. Lagou V, Reedik Mägi R, Hottenga JJ, Grallert H, Perry JRB, Bouatia-Naji N, Marullo L, Rybin D, Janssen R (2018) Fasting glucose and insulin variability: sex-dimorphic genetic effects and novel loci (in preparation) Google Scholar
  41. Lauenborg J, Grarup N, Damm P, Borch-Johnsen K, Jørgensen T, Pedersen O, Hansen T (2009) Common type 2 diabetes risk gene variants associate with gestational diabetes. J Clin Endocrinol Metab 94(1):145–150Google Scholar
  42. Li C, Qiao B, Zhan Y, Chen ZJ, Sun L, Zhang J, Zhao L, Gao Q (2013) Association between genetic variations in MTNR1A and MTNR1B genes and gestational diabetes mellitus in Han Chinese women. Gynecol Obstet Invest 76(4):221–227Google Scholar
  43. Li J, Chen YP, Dong YP, Yu CH, Lu YP, Xiao XM, Hocher B (2014) The impact of umbilical blood flow regulation on fetal development differs in diabetic and non-diabetic pregnancy. Kidney Blood Press Res 39(4):369–377Google Scholar
  44. Li C, Qiao B, Qi W, Zhan Y, Ma C, Zhao L, Li G (2016) Association of macrophage migration inhibitory factor polymorphisms with gestational diabetes mellitus in han Chinese women. Gynecol Obstet Invest 81(1):84–89Google Scholar
  45. Liao S, Liu Y, Tan Y, Gan L, Mei J, Song W et al (2012) Association of genetic variants of melatonin receptor 1B with gestational plasma glucose level and risk of glucose intolerance in pregnant Chinese women. PLoS One 7(7):e40113Google Scholar
  46. Liao S, Liu Y, Chen X, Tan Y, Mei J, Song W, Gan L, Wang H, Yin S, Dong X, Chi S, Deng S (2015) The impact of genetic variants for different physiological characterization of type 2 diabetes loci on gestational insulin signaling in nondiabetic pregnant Chinese women. Reprod Sci 22(11):1421–1428Google Scholar
  47. Macias-Gonzalez M, Cardona F, Queipo-Ortuño M, Bernal R, Martin M, Tinahones FJ (2008) PPARgamma mRNA expression is reduced in peripheral blood mononuclear cells after fat overload in patients with metabolic syndrome. J Nutr 138(5):903–907Google Scholar
  48. Mahajan A, Taliun D, Thurner M, Robertson NR, Torres JM, Rayner NW, Payne AJ, Steinthorsdottir V, Scott RA, Grarup N, Cook JP, Schmidt EM, Wuttke M, Sarnowski C, Mägi R, Nano J, Gieger C, Trompet S, Lecoeur C, Preuss MH, Prins BP, Guo X, Bielak LF, Below JE, Bowden DW, Chambers JC, Kim YJ, Ng MCY, Petty LE, Sim X, Zhang W, Bennett AJ, Bork-Jensen J, Brummett CM, Canouil M, Ec Kardt KU, Fischer K, Kardia SLR, Kronenberg F, Läll K, Liu CT, Locke AE, Luan J, Ntalla I, Nylander V, Schönherr S, Schurmann C, Yengo L, Bottinger EP, Brandslund I, Christensen C, Dedoussis G, Florez JC, Ford I, Franco OH, Frayling TM, Giedraitis V, Hackinger S, Hattersley AT, Herder C, Ikram MA, Ingelsson M, Jørgensen ME, Jørgensen T, Kriebel J, Kuusisto J, Ligthart S, Lindgren CM, Linneberg A, Lyssenko V, Mamakou V, Meitinger T, Mohlke KL, Morris AD, Nadkarni G, Pankow JS, Peters A, Sattar N, Stančáková A, Strauch K, Taylor KD, Thorand B, Thorleifsson G, Thorsteinsdottir U, Tuomilehto J, Witte DR, Dupuis J, Peyser PA, Zeggini E, Loos RJF, Froguel P, Ingelsson E, Lind L, Groop L, Laakso M, Collins FS, Jukema JW, Palmer CNA, Grallert H, Metspalu A, Dehghan A, Köttgen A, Abecasis GR, Meigs JB, Rotter JI, Marchini J, Pedersen O, Hansen T, Langenberg C, Wareham NJ, Stefansson K, Gloyn AL, Morris AP, Boehnke M, McCarthy MI (2018) Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps. Nat Genet. 50(11):1505–1513Google Scholar
  49. Manning AK, Hivert MF, Scott RA, Grimsby JL, Bouatia-Naji N, Chen H, Rybin D, Liu CT, Bielak LF, Prokopenko I, Amin N, Barnes D, Cadby G, Hottenga JJ, Ingelsson E, Jackson AU, Johnson T, Kanoni S, Ladenvall C, Lagou V, Lahti J, Lecoeur C, Liu Y, Martinez-Larrad MT, Montasser ME, Navarro P, Perry JR, Rasmussen-Torvik LJ, Salo P, Sattar N, Shungin D, Strawbridge RJ, Tanaka T, van Duijn CM, An P, de Andrade M, Andrews JS, Aspelund T, Atalay M, Aulchenko Y, Balkau B, Bandinelli S, Beckmann JS, Beilby JP, Bellis C, Bergman RN, Blangero J, Boban M, Boehnke M, Boerwinkle E, Bonnycastle LL, Boomsma DI, Borecki IB, Böttcher Y, Bouchard C, Brunner E, Budimir D, Campbell H, Carlson O, Chines PS, Clarke R, Collins FS, Corbatón-Anchuelo A, Couper D, de Faire U, Dedoussis GV, Deloukas P, Dimitriou M, Egan JM, Eiriksdottir G, Erdos MR, Eriksson JG, Eury E, Ferrucci L, Ford I, Forouhi NG, Fox CS, Franzosi MG, Franks PW, Frayling TM, Froguel P, Galan P, de Geus E, Gigante B, Glazer NL, Goel A, Groop L, Gudnason V, Hallmans G, Hamsten A, Hansson O, Harris TB, Hayward C, Heath S, Hercberg S, Hicks AA, Hingorani A, Hofman A, Hui J, Hung J, Jarvelin MR, Jhun MA, Johnson PC, Jukema JW, Jula A, Kao WH, Kaprio J, Kardia SL, Keinanen-Kiukaanniemi S, Kivimaki M, Kolcic I, Kovacs P, Kumari M, Kuusisto J, Kyvik KO, Laakso M, Lakka T, Lannfelt L, Lathrop GM, Launer LJ, Leander K, Li G, Lind L, Lindstrom J, Lobbens S, Loos RJ, Luan J, Lyssenko V, Mägi R, Magnusson PK, Marmot M, Meneton P, Mohlke KL, Mooser V, Morken MA, Miljkovic I, Narisu N, O’Connell J, Ong KK, Oostra BA, Palmer LJ, Palotie A, Pankow JS, Peden JF, Pedersen NL, Pehlic M, Peltonen L, Penninx B, Pericic M, Perola M, Perusse L, Peyser PA, Polasek O, Pramstaller PP, Province MA, Räikkönen K, Rauramaa R, Rehnberg E, Rice K, Rotter JI, Rudan I, Ruokonen A, Saaristo T, Sabater-Lleal M, Salomaa V, Savage DB, Saxena R, Schwarz P, Seedorf U, Sennblad B, Serrano-Rios M, Shuldiner AR, Sijbrands EJ, Siscovick DS, Smit JH, Small KS, Smith NL, Smith AV, Stančáková A, Stirrups K, Stumvoll M, Sun YV, Swift AJ, Tönjes A, Tuomilehto J, Trompet S, Uitterlinden AG, Uusitupa M, Vikström M, Vitart V, Vohl MC, Voight BF, Vollenweider P, Waeber G, Waterworth DM, Watkins H, Wheeler E, Widen E, Wild SH, Willems SM, Willemsen G, Wilson JF, Witteman JC, Wright AF, Yaghootkar H, Zelenika D, Zemunik T, Zgaga L, Wareham NJ, McCarthy MI, Barroso I, Watanabe RM, Florez JC, Dupuis J, Meigs JB, Langenberg C, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium; Multiple Tissue Human Expression Resource (MUTHER) Consortium (2012) A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat Genet 44(6):659–669Google Scholar
  50. Mei J, Liao S, Liu Y, Tan Y, Wang H, Liang Y et al (2015) Association of variants in CDKN2A/2B and CDKAL1 genes with gestational insulin sensitivity and disposition in pregnant Han Chinese women. J Diabetes Investig 6(3):295–301Google Scholar
  51. Monroy VS, Díaz CA, Trenado LM, Peralta JM, Soto SM (2014) Thr130Ile polymorphism of HNF4A gene is associated with gestational diabetes mellitus in Mexican population. J Investig Med 62(3):632–634Google Scholar
  52. Morris AP, Voight BF, Teslovich TM, Ferreira T, Segre AV, Steinthorsdottir V, Strawbridge RJ, Khan H, Grallert H, Mahajan A, Prokopenko I, Kang HM, Dina C, Esko T, Fraser RM, Kanoni S, Kumar A, Lagou V, Langenberg C, Luan J, Lindgren CM, Müller-Nurasyid M, Pechlivanis S, Rayner NW, Scott LJ, Wiltshire S, Yengo L, Kinnunen L, Rossin EJ, Raychaudhuri S, Johnson AD, Dimas AS, Loos RJ, Vedantam S, Chen H, Florez JC, Fox C, Liu CT, Rybin D, Couper DJ, Kao WH, Li M, Cornelis MC, Kraft P, Sun Q, van Dam RM, Stringham HM, Chines PS, Fischer K, Fontanillas P, Holmen OL, Hunt SE, Jackson AU, Kong A, Lawrence R, Meyer J, Perry JR, Platou CG, Potter S, Rehnberg E, Robertson N, Sivapalaratnam S, Stančáková A, Stirrups K, Thorleifsson G, Tikkanen E, Wood AR, Almgren P, Atalay M, Benediktsson R, Bonnycastle LL, Burtt N, Carey J, Charpentier G, Crenshaw AT, Doney AS, Dorkhan M, Edkins S, Emilsson V, Eury E, Forsen T, Gertow K, Gigante B, Grant GB, Groves CJ, Guiducci C, Herder C, Hreidarsson AB, Hui J, James A, Jonsson A, Rathmann W, Klopp N, Kravic J, Krjutškov K, Langford C, Leander K, Lindholm E, Lobbens S, Männistö S, Mirza G, Mühleisen TW, Musk B, Parkin M, Rallidis L, Saramies J, Sennblad B, Shah S, Sigurðsson G, Silveira A, Steinbach G, Thorand B, Trakalo J, Veglia F, Wennauer R, Winckler W, Zabaneh D, Campbell H, van Duijn C, Uitterlinden AG, Hofman A, Sijbrands E, Abecasis GR, Owen KR, Zeggini E, Trip MD, Forouhi NG, Syvänen AC, Eriksson JG, Peltonen L, Nöthen MM, Balkau B, Palmer CN, Lyssenko V, Tuomi T, Isomaa B, Hunter DJ, Qi L, Shuldiner AR, Roden M, Barroso I, Wilsgaard T, Beilby J, Hovingh K, Price JF, Wilson JF, Rauramaa R, Lakka TA, Lind L, Dedoussis G, Njølstad I, Pedersen NL, Khaw KT, Wareham NJ, Keinanen-Kiukaanniemi SM, Saaristo TE, Korpi-Hyövälti E, Saltevo J, Laakso M, Kuusisto J, Metspalu A, Collins FS, Mohlke KL, Bergman RN, Tuomilehto J, Boehm BO, Gieger C, Hveem K, Cauchi S, Froguel P, Baldassarre D, Tremoli E, Humphries SE, Saleheen D, Danesh J, Ingelsson E, Ripatti S, Salomaa V, Erbel R, Jöckel KH, Moebus S, Peters A, Illig T, de Faire U, Hamsten A, Morris AD, Donnelly PJ, Frayling TM, Hattersley AT, Boerwinkle E, Melander O, Kathiresan S, Nilsson PM, Deloukas P, Thorsteinsdottir U, Groop LC, Stefansson K, Hu F, Pankow JS, Dupuis J, Meigs JB, Altshuler D, Boehnke M, McCarthy MI, Wellcome Trust Case Control Consortium; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) Investigators; Genetic Investigation of ANthropometric Traits (GIANT) Consortium; Asian Genetic Epidemiology Network–Type 2 Diabetes (AGEN-T2D) Consortium; South Asian Type 2 Diabetes (SAT2D) Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium (2012) Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet 44(9):981–990Google Scholar
  53. Nair AV, Hocher B, Verkaart S, van Zeeland F, Pfab T, Slowinski T, Chen YP, Schlingmann KP, Schaller A, Gallati S, Bindels RJ, Konrad M, Hoenderop JG (2012) Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy. Proc Natl Acad Sci USA 109(28):11324–11329Google Scholar
  54. Ohara-Imaizumi M, Kim H, Yoshida M, Fujiwara T, Aoyagi K, Toyofuku Y, Nakamichi Y, Nishiwaki C, Okamura T, Uchida T, Fujitani Y, Akagawa K, Kakei M, Watada H, German MS, Nagamatsu S (2013) Serotonin regulates glucose-stimulated insulin secretion from pancreatic β cells during pregnancy. Proc Natl Acad Sci USA 110(48):19420–19425Google Scholar
  55. Pagán A, Sabater-Molina M, Olza J, Prieto-Sánchez MT, Blanco-Carnero JE, Parrilla JJ, Gil Á, Larqué E (2014) A gene variant in the transcription factor 7-like 2 (TCF7L2) is associated with an increased risk of gestational diabetes mellitus. Eur J Obstet Gynecol Reprod Biol 180:77–82Google Scholar
  56. Pappa KI, Gazouli M, Economou K, Daskalakis G, Anastasiou E, Anagnou NP, Antsaklis A (2011) Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population. Gynecol Endocrinol 27(4):267–272Google Scholar
  57. Pappa KI, Gazouli M, Anastasiou E, Iliodromiti Z, Antsaklis A, Anagnou NP (2013a) The major circadian pacemaker ARNT-like protein-1 (BMAL1) is associated with susceptibility to gestational diabetes mellitus. Diabetes Res Clin Pract 99(2):151–157Google Scholar
  58. Pappa KI, Gazouli M, Anastasiou E, Iliodromiti Z, Antsaklis A, Anagnou NP (2013b) Circadian clock gene expression is impaired in gestational diabetes mellitus. Gynecol Endocrinol 29(4):331–335Google Scholar
  59. Pappa KI, Gazouli M, Anastasiou E, Loutradis D, Anagnou NP (2017) The Q192R polymorphism of the paraoxonase-1 (PON1) gene is associated with susceptibility to gestational diabetes mellitus in the Greek population. Gynecol Endocrinol 33(8):617–620Google Scholar
  60. Pawlik A, Teler J, Maciejewska A, Sawczuk M, Safranow K, Dziedziejko V (2017) Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus. J Assist Reprod Genet 34(4):511–516Google Scholar
  61. Ping F, Xiang HD, Li M, Li W, Liu JT, Nie M, Hui YC (2012) Effects of variation in retinol binding protein 4 gene and adipose specific expression of gestational diabetes in Beijing, China. Diabetes Res Clin Pract 97(2):283–289Google Scholar
  62. Powe CE, Nodzenski M, Talbot O, Allard C, Briggs C, Leya MV, Perron P, Bouchard L, Florez JC, Scholtens DM, Lowe WL Jr, Hivert MF (2018) Genetic determinants of glycemic traits and the risk of gestational diabetes mellitus. Diabetes.  https://doi.org/10.2337/db18-0203 Google Scholar
  63. Prokopenko I, Poon W, Mägi R, Prasad BR, Salehi SA, Almgren P, Osmark P, Bouatia-Naji N, Wierup N, Fall T, Stančáková A, Barker A, Lagou V, Osmond C, Xie W, Lahti J, Jackson AU, Cheng YC, Liu J, O’Connell JR, Blomstedt PA, Fadista J, Alkayyali S, Dayeh T, Ahlqvist E, Taneera J, Lecoeur C, Kumar A, Hansson O, Hansson K, Voight BF, Kang HM, Levy-Marchal C, Vatin V, Palotie A, Syvänen AC, Mari A, Weedon MN, Loos RJ, Ong KK, Nilsson P, Isomaa B, Tuomi T, Wareham NJ, Stumvoll M, Widen E, Lakka TA, Langenberg C, Tönjes A, Rauramaa R, Kuusisto J, Frayling TM, Froguel P, Walker M, Eriksson JG, Ling C, Kovacs P, Ingelsson E, McCarthy MI, Shuldiner AR, Silver KD, Laakso M, Groop L, Lyssenko V (2014) A central role for GRB10 in regulation of islet function in man. PLoS Genet 10(4):e1004235Google Scholar
  64. Rafiq S, Melzer D, Weedon MN, Lango H, Saxena R, Scott LJ, Palmer CN, Morris AD, McCarthy MI, Ferrucci L, Hattersley AT, Zeggini E, Frayling TM, DIAGRAM Consortium (2008) Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes. Diabetologia 51(12):2205–2213Google Scholar
  65. Rahmannezhad G, Mashayekhi FJ, Goodarzi MT, Rezvanfar MR, Sadeghi A (2016) Association between vitamin D receptor ApaI and TaqI gene polymorphisms and gestational diabetes mellitus in an Iranian pregnant women population. Gene 581(1):43–47Google Scholar
  66. Reichetzeder C, Dwi Putra SE, Pfab T, Slowinski T, Neuber C, Kleuser B, Hocher B (2016) Increased global placental DNA methylation levels are associated with gestational diabetes. Clin Epigenet. 26(8):82Google Scholar
  67. Retnakaran R, Hanley AJ, Sermer M, Zinman B (2005) The impact of insulin resistance on proinsulin secretion in pregnancy: hyperproinsulinemia is not a feature of gestational diabetes. Diabetes Care 28(11):2710–2715Google Scholar
  68. Retnakaran R, Zinman B, Connelly PW, Sermer M, Hanley AJ (2006) Impaired glucose tolerance of pregnancy is a heterogeneous metabolic disorder as defined by the glycemic response to the oral glucose tolerance test. Diabetes Care 29(1):57–62Google Scholar
  69. Richard MW, Hooman A, Xiang AH, Xiang AH, Trigo E, Hartiala J, Lawrence JM, Buchanan TA (2007) Transcription factor 7-like 2 (TCF7L2) is associated with gestational diabetes mellitus and interacts with adiposity to alter insulin secretion in Mexican Americans. Diabetes 56(5):1481–1485Google Scholar
  70. Riskin-Mashiah S, Younes G, Damti A, Auslender R (2009) First-trimester fasting hyperglycemia and adverse pregnancy outcomes. Diabetes Care 32(9):1639–1643Google Scholar
  71. Saucedo R, Zarate A, Basurto L, Hernandez M, Puello E, Mendoza-Lorenzo P, Ostrosky-Wegman P (2014) RBP4 gene variants are associated with insulin resistance in women with previous gestational diabetes. Dis Markers 2014:269208Google Scholar
  72. Saxena R, Hivert MF, Langenberg C, Tanaka T, Pankow JS, Vollenweider P, Lyssenko V, Bouatia-Naji N, Dupuis J, Jackson AU, Kao WH, Li M, Glazer NL, Manning AK, Luan J, Stringham HM, Prokopenko I, Johnson T, Grarup N, Boesgaard TW, Lecoeur C, Shrader P, O’Connell J, Ingelsson E, Couper DJ, Rice K, Song K, Andreasen CH, Dina C, Köttgen A, Le Bacquer O, Pattou F, Taneera J, Steinthorsdottir V, Rybin D, Ardlie K, Sampson M, Qi L, van Hoek M, Weedon MN, Aulchenko YS, Voight BF, Grallert H, Balkau B, Bergman RN, Bielinski SJ, Bonnefond A, Bonnycastle LL, Borch-Johnsen K, Böttcher Y, Brunner E, Buchanan TA, Bumpstead SJ, Cavalcanti-Proença C, Charpentier G, Chen YD, Chines PS, Collins FS, Cornelis M, Crawford G, Delplanque J, Doney A, Egan JM, Erdos MR, Firmann M, Forouhi NG, Fox CS, Goodarzi MO, Graessler J, Hingorani A, Isomaa B, Jørgensen T, Kivimaki M, Kovacs P, Krohn K, Kumari M, Lauritzen T, Lévy-Marchal C, Mayor V, McAteer JB, Meyre D, Mitchell BD, Mohlke KL, Morken MA, Narisu N, Palmer CN, Pakyz R, Pascoe L, Payne F, Pearson D, Rathmann W, Sandbaek A, Sayer AA, Scott LJ, Sharp SJ, Sijbrands E, Singleton A, Siscovick DS, Smith NL, Sparsø T, Swift AJ, Syddall H, Thorleifsson G, Tönjes A, Tuomi T, Tuomilehto J, Valle TT, Waeber G, Walley A, Waterworth DM, Zeggini E, Zhao JH, Illig T, Wichmann HE, Wilson JF, van Duijn C, Hu FB, Morris AD, Frayling TM, Hattersley AT, Thorsteinsdottir U, Stefansson K, Nilsson P, Syvänen AC, Shuldiner AR, Walker M, Bornstein SR, Schwarz P, Williams GH, Nathan DM, Kuusisto J, Laakso M, Cooper C, Marmot M, Ferrucci L, Mooser V, Stumvoll M, Loos RJ, Altshuler D, Psaty BM, Rotter JI, Boerwinkle E, Hansen T, Pedersen O, Florez JC, McCarthy MI, Boehnke M, Barroso I, Sladek R, Froguel P, Meigs JB, Groop L, Wareham NJ, Watanabe RM, GIANT consortium, MAGIC investigators, (2010) Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat Genet 42(2):142–148Google Scholar
  73. Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, Mägi R, Strawbridge RJ, Rehnberg E, Gustafsson S, Kanoni S, Rasmussen-Torvik LJ, Yengo L, Lecoeur C, Shungin D, Sanna S, Sidore C, Johnson PC, Jukema JW, Johnson T, Mahajan A, Verweij N, Thorleifsson G, Hottenga JJ, Shah S, Smith AV, Sennblad B, Gieger C, Salo P, Perola M, Timpson NJ, Evans DM, Pourcain BS, Wu Y, Andrews JS, Hui J, Bielak LF, Zhao W, Horikoshi M, Navarro P, Isaacs A, O’Connell JR, Stirrups K, Vitart V, Hayward C, Esko T, Mihailov E, Fraser RM, Fall T, Voight BF, Raychaudhuri S, Chen H, Lindgren CM, Morris AP, Rayner NW, Robertson N, Rybin D, Liu CT, Beckmann JS, Willems SM, Chines PS, Jackson AU, Kang HM, Stringham HM, Song K, Tanaka T, Peden JF, Goel A, Hicks AA, An P, Müller-Nurasyid M, Franco-Cereceda A, Folkersen L, Marullo L, Jansen H, Oldehinkel AJ, Bruinenberg M, Pankow JS, North KE, Forouhi NG, Loos RJ, Edkins S, Varga TV, Hallmans G, Oksa H, Antonella M, Nagaraja R, Trompet S, Ford I, Bakker SJ, Kong A, Kumari M, Gigante B, Herder C, Munroe PB, Caulfield M, Antti J, Mangino M, Small K, Miljkovic I, Liu Y, Atalay M, Kiess W, James AL, Rivadeneira F, Uitterlinden AG, Palmer CN, Doney AS, Willemsen G, Smit JH, Campbell S, Polasek O, Bonnycastle LL, Hercberg S, Dimitriou M, Bolton JL, Fowkes GR, Kovacs P, Lindström J, Zemunik T, Bandinelli S, Wild SH, Basart HV, Rathmann W, Grallert H, Maerz W, Kleber ME, Boehm BO, Peters A, Pramstaller PP, Province MA, Borecki IB, Hastie ND, Rudan I, Campbell H, Watkins H, Farrall M, Stumvoll M, Ferrucci L, Waterworth DM, Bergman RN, Collins FS, Tuomilehto J, Watanabe RM, de Geus EJ, Penninx BW, Hofman A, Oostra BA, Psaty BM, Vollenweider P, Wilson JF, Wright AF, Hovingh GK, Metspalu A, Uusitupa M, Magnusson PK, Kyvik KO, Kaprio J, Price JF, Dedoussis GV, Deloukas P, Meneton P, Lind L, Boehnke M, Shuldiner AR, van Duijn CM, Morris AD, Toenjes A, Peyser PA, Beilby JP, Körner A, Kuusisto J, Laakso M, Bornstein SR, Schwarz PE, Lakka TA, Rauramaa R, Adair LS, Smith GD, Spector TD, Illig T, de Faire U, Hamsten A, Gudnason V, Kivimaki M, Hingorani A, Keinanen-Kiukaanniemi SM, Saaristo TE, Boomsma DI, Stefansson K, van der Harst P, Dupuis J, Pedersen NL, Sattar N, Harris TB, Cucca F, Ripatti S, Salomaa V, Mohlke KL, Balkau B, Froguel P, Pouta A, Jarvelin MR, Wareham NJ, Bouatia-Naji N, McCarthy MI, Franks PW, Meigs JB, Teslovich TM, Florez JC, Langenberg C, Ingelsson E, Prokopenko I, Barroso I, DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium (2012) Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet 44(9):991–1005Google Scholar
  74. Shaat N, Ekelund M, Lernmark A, Ivarsson S, Almgren P, Berntorp K, Groop L (2005) Association of the E23 K polymorphism in the KCNJ11 gene with gestational diabetes mellitus. Diabetologia 48(12):2544–2551Google Scholar
  75. Shaat N, Lernmark A, Karlsson E, Ivarsson S, Parikh H, Berntorp K, Groop L (2007) A variant in the transcription factor 7-like 2 (TCF7L2) gene is associated with an increased risk of gestational diabetes mellitus. Diabetologia 50(5):972–979Google Scholar
  76. Soranzo N, Sanna S, Wheeler E, Gieger C, Radke D, Dupuis J, Bouatia-Naji N, Langenberg C, Prokopenko I, Stolerman E, Sandhu MS, Heeney MM, Devaney JM, Reilly MP, Ricketts SL, Stewart AF, Voight BF, Willenborg C, Wright B, Altshuler D, Arking D, Balkau B, Barnes D, Boerwinkle E, Böhm B, Bonnefond A, Bonnycastle LL, Boomsma DI, Bornstein SR, Böttcher Y, Bumpstead S, Burnett-Miller MS, Campbell H, Cao A, Chambers J, Clark R, Collins FS, Coresh J, de Geus EJ, Dei M, Deloukas P, Döring A, Egan JM, Elosua R, Ferrucci L, Forouhi N, Fox CS, Franklin C, Franzosi MG, Gallina S, Goel A, Graessler J, Grallert H, Greinacher A, Hadley D, Hall A, Hamsten A, Hayward C, Heath S, Herder C, Homuth G, Hottenga JJ, Hunter-Merrill R, Illig T, Jackson AU, Jula A, Kleber M, Knouff CW, Kong A, Kooner J, Köttgen A, Kovacs P, Krohn K, Kühnel B, Kuusisto J, Laakso M, Lathrop M, Lecoeur C, Li M, Li M, Loos RJ, Luan J, Lyssenko V, Mägi R, Magnusson PK, Mälarstig A, Mangino M, Martínez-Larrad MT, März W, McArdle WL, McPherson R, Meisinger C, Meitinger T, Melander O, Mohlke KL, Mooser VE, Morken MA, Narisu N, Nathan DM, Nauck M, O’Donnell C, Oexle K, Olla N, Pankow JS, Payne F, Peden JF, Pedersen NL, Peltonen L, Perola M, Polasek O, Porcu E, Rader DJ, Rathmann W, Ripatti S, Rocheleau G, Roden M, Rudan I, Salomaa V, Saxena R, Schlessinger D, Schunkert H, Schwarz P, Seedorf U, Selvin E, Serrano-Ríos M, Shrader P, Silveira A, Siscovick D, Song K, Spector TD, Stefansson K, Steinthorsdottir V, Strachan DP, Strawbridge R, Stumvoll M, Surakka I, Swift AJ, Tanaka T, Teumer A, Thorleifsson G, Thorsteinsdottir U, Tönjes A, Usala G, Vitart V, Völzke H, Wallaschofski H, Waterworth DM, Watkins H, Wichmann HE, Wild SH, Willemsen G, Williams GH, Wilson JF, Winkelmann J, Wright AF, Zabena C, Zhao JH, Epstein SE, Erdmann J, Hakonarson HH, Kathiresan S, Khaw KT, Roberts R, Samani NJ, Fleming MD, Sladek R, Abecasis G, Boehnke M, Froguel P, Groop L, McCarthy MI, Kao WH, Florez JC, Uda M, Wareham NJ, Barroso I, Meigs JB, WTCCC (2010) Common variants at 10 genomic loci influence hemoglobin A1 (C) levels via glycemic and nonglycemic pathways. Diabetes. 59(12):3229–3239Google Scholar
  77. Sparsø T, Bonnefond A, Andersson E, Bouatia-Naji N, Holmkvist J, Wegner L, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, Nica A, Wheeler E, Chen H, Voight BF, Taneera J, Kanoni S, Peden JF, Turrini F, Gustafsson S, Zabena C, Almgren P, Barker DJ, Barnes D, Dennison EM, Eriksson JG, Eriksson P, Eury E, Folkersen L, Fox CS, Frayling TM, Goel A, Gu HF, Horikoshi M, Isomaa B, Jackson AU, Jameson KA, Kajantie E, Kerr-Conte J, Kuulasmaa T, Kuusisto J, Loos RJ, Luan J, Makrilakis K, Manning AK, Martínez-Larrad MT, Narisu N, Nastase Mannila M, Ohrvik J, Osmond C, Pascoe L, Payne F, Sayer AA, Sennblad B, Silveira A, Stancáková A, Stirrups K, Swift AJ, Syvänen AC, Tuomi T, Hooft FM, Walker M, Weedon MN, Xie W, Zethelius B, Ongen H, Mälarstig A, Hopewell JC, Saleheen D, Chambers J, Parish S, Danesh J, Kooner J, Ostenson CG, Lind L, Cooper CC, Serrano-Ríos M, Ferrannini E, Forsen TJ, Clarke R, Franzosi MG, Seedorf U, Watkins H, Froguel P, Johnson P, Deloukas P, Collins FS, Laakso M, Dermitzakis ET, Boehnke M, McCarthy MI, Wareham NJ, Groop L, Pattou F, Gloyn AL, Dedoussis GV, Lyssenko V, Meigs JB, Barroso I, Watanabe RM, Ingelsson E, Langenberg C, Hamsten A, Florez JC, DIAGRAM Consortium; GIANT Consortium; MuTHER Consortium; CARDIoGRAM Consortium; C4D Consortium, DIAGRAM Consortium; GIANT Consortium; MuTHER Consortium; CARDIoGRAM Consortium; C4D Consortium (2009) G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release studies involving 19,605 Europeans. Diabetes 58(6):1450–1456Google Scholar
  78. Stancáková A, Kuulasmaa T, Paananen J, Jackson AU, Bonnycastle LL, Collins FS, Boehnke M, Kuusisto J, Laakso M (2009) Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men. Diabetes 58(9):2129–2136Google Scholar
  79. Strawbridge RJ, Dupuis J, Prokopenko I, Barker A, Ahlqvist T, Rybin D, Petrie JR, Travers ME, Bouatia-Naji N, Dimas AS, Nica A, Wheeler E, Chen H, Voight BF, Taneera J, Kanoni S, Peden JF, Turrini F, Gustafsson S, Zabena C, Almgren P, Barker DJ, Barnes D, Dennison EM, Eriksson JG, Eriksson P, Eury E, Folkersen L, Fox CS, Frayling TM, Goel A, Gu HF, Horikoshi M, Isomaa B, Jackson AU, Jameson KA, Kajantie E, Kerr-Conte J, Kuulasmaa T, Kuusisto J, Loos RJ, Luan J, Makrilakis K, Manning AK, Martínez-Larrad MT, Narisu N, Nastase Mannila M, Ohrvik J, Osmond C, Pascoe L, Payne F, Sayer AA, Sennblad B, Silveira A, Stancáková A, Stirrups K, Swift AJ, Syvänen AC, Tuomi T, van’t Hooft FM, Walker M, Weedon MN, Xie W, Zethelius B, Ongen H, Mälarstig A, Hopewell JC, Saleheen D, Chambers J, Parish S, Danesh J, Kooner J, Ostenson CG, Lind L, Cooper CC, Serrano-Ríos M, Ferrannini E, Forsen TJ, Clarke R, Franzosi MG, Seedorf U, Watkins H, Froguel P, Johnson P, Deloukas P, Collins FS, Laakso M, Dermitzakis ET, Boehnke M, McCarthy MI, Wareham NJ, Groop L, Pattou F, Gloyn AL, Dedoussis GV, Lyssenko V, Meigs JB, Barroso I, Watanabe RM, Ingelsson E, Langenberg C, Hamsten A, Florez JC, DIAGRAM Consortium; GIANT Consortium; MuTHER Consortium; CARDIoGRAM Consortium; C4D Consortium (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(10):2624–2634Google Scholar
  80. Stuebe AM, Lyon H, Herring AH, Ghosh J, Wise A, North KE, Siega-Riz AM (2010) Obesity and diabetes genetic variants associated with gestational weight gain. Am J Obstet Gynecol 203(3):283.e1–283.e17Google Scholar
  81. Stuebe AM, Wise A, Nguyen T, Herring A, North KE, Siega-Riz AM (2014) Maternal genotype and gestational diabetes. Am J Perinatol 31(1):69–76Google Scholar
  82. Tarquini F, Picchiassi E, Centra M, Pennacchi L, Bini V, Cappuccini B, Torlone E, Coata G, Di Renzo G, Brancorsini S (2015) Body mass index associated to rs2021966 ENPP1 polymorphism increases the risk for gestational diabetes mellitus. Gynecol Endocrinol 31(1):83–86Google Scholar
  83. Tok EC, Ertunc D, Bilgin O, Erdal EM, Kaplanoglu M, Dilek S (2006) Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus. Am J Obstet Gynecol 194(3):868–872Google Scholar
  84. Urbanek M, Hayes MG, Lee H, Freathy RM, Lowe LP, Ackerman C, Jafari N, Dyer AR, Cox NJ, Dunger DB, Hattersley AT, Metzger BE, Lowe WL Jr (2012) The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy. PLoS One 7(3):e32958Google Scholar
  85. Vella CA, Burgos X, Ellis CJ, Zubia RY, Ontiveros D, Reyes H, Lozano C (2013) Associations of insulin resistance with cardiovascular risk factors and inflammatory cytokines in normal-weight Hispanic women. Diabetes Care 36(5):1377–1383Google Scholar
  86. Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu CT, Hong J, Jensen RA, Rice K, Morris AP, Mägi R, Tönjes A, Prokopenko I, Kleber ME, Delgado G, Silbernagel G, Jackson AU, Appel EV, Grarup N, Lewis JP, Montasser ME, Landenvall C, Staiger H, Luan J, Frayling TM, Weedon MN, Xie W, Morcillo S, Martínez-Larrad MT, Biggs ML, Chen YD, Corbaton-Anchuelo A, Færch K, Gómez-Zumaquero JM, Goodarzi MO, Kizer JR, Koistinen HA, Leong A, Lind L, Lindgren C, Machicao F, Manning AK, Martín-Núñez GM, Rojo-Martínez G, Rotter JI, Siscovick DS, Zmuda JM, Zhang Z, Serrano-Rios M, Smith U, Soriguer F, Hansen T, Jørgensen TJ, Linnenberg A, Pedersen O, Walker M, Langenberg C, Scott RA, Wareham NJ, Fritsche A, Häring HU, Stefan N, Groop L, O’Connell JR, Boehnke M, Bergman RN, Collins FS, Mohlke KL, Tuomilehto J, März W, Kovacs P, Stumvoll M, Psaty BM, Kuusisto J, Laakso M, Meigs JB, Dupuis J, Ingelsson E, Florez JC (2016) Genome-wide association study of the modified stumvoll insulin sensitivity index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci. Diabetes 65(10):3200–3211Google Scholar
  87. Wang Y, Nie M, Li W, Ping F, Hu Y, Ma L, Gao J, Liu J (2011) Association of six single nucleotide polymorphisms with gestational diabetes mellitus in a Chinese population. PLoS One 6(11):e26953Google Scholar
  88. Weedon MN, Frayling TM, Shields B, Knight B, Turner T, Metcalf BS, Voss L, Wilkin TJ, McCarthy A, Ben-Shlomo Y, Davey Smith G, Ring S, Jones R, Golding J, Byberg L, Mann V, Axelsson T, Syvänen AC, Leon D, Hattersley AT (2005) Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. Diabetes 54(2):576–581Google Scholar
  89. Wessel J, Chu AY, Willems SM, Wang S, Yaghootkar H, Brody JA et al (2015) Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility. Nat Commun 29(6):5897Google Scholar
  90. Wheeler E, Leong A, Liu CT, Hivert MF, Strawbridge RJ, Podmore C, Li M, Yao J, Sim X, Hong J, Chu AY, Zhang W, Wang X, Chen P, Maruthur NM, Porneala BC, Sharp SJ, Jia Y, Kabagambe EK, Chang LC, Chen WM, Elks CE, Evans DS, Fan Q, Giulianini F, Go MJ, Hottenga JJ, Hu Y, Jackson AU, Kanoni S, Kim YJ, Kleber ME, Ladenvall C, Lecoeur C, Lim SH, Lu Y, Mahajan A, Marzi C, Nalls MA, Navarro P, Nolte IM, Rose LM, Rybin DV, Sanna S, Shi Y, Stram DO, Takeuchi F, Tan SP, van der Most PJ, Van Vliet-Ostaptchouk JV, Wong A, Yengo L, Zhao W, Goel A, Martinez Larrad MT, Radke D, Salo P, Tanaka T, van Iperen EPA, Abecasis G, Afaq S, Alizadeh BZ, Bertoni AG, Bonnefond A, Böttcher Y, Bottinger EP, Campbell H, Carlson OD, Chen CH, Cho YS, Garvey WT, Gieger C, Goodarzi MO, Grallert H, Hamsten A, Hartman CA, Herder C, Hsiung CA, Huang J, Igase M, Isono M, Katsuya T, Khor CC, Kiess W, Kohara K, Kovacs P, Lee J, Lee WJ, Lehne B, Li H, Liu J, Lobbens S, Luan J, Lyssenko V, Meitinger T, Miki T, Miljkovic I, Moon S, Mulas A, Müller G, Müller-Nurasyid M, Nagaraja R, Nauck M, Pankow JS, Polasek O, Prokopenko I, Ramos PS, Rasmussen-Torvik L, Rathmann W, Rich SS, Robertson NR, Roden M, Roussel R, Rudan I, Scott RA, Scott WR, Sennblad B, Siscovick DS, Strauch K, Sun L, Swertz M, Tajuddin SM, Taylor KD, Teo YY, Tham YC, Tönjes A, Wareham NJ, Willemsen G, Wilsgaard T, Hingorani AD, Egan J, Ferrucci L, Hovingh GK, Jula A, Kivimaki M, Kumari M, Njølstad I, Palmer CNA, Serrano Ríos M, Stumvoll M, Watkins H, Aung T, Blüher M, Boehnke M, Boomsma DI, Bornstein SR, Chambers JC, Chasman DI, Chen YI, Chen YT, Cheng CY, Cucca F, de Geus EJC, Deloukas P, Evans MK, Fornage M, Friedlander Y, Froguel P, Groop L, Gross MD, Harris TB, Hayward C, Heng CK, Ingelsson E, Kato N, Kim BJ, Koh WP, Kooner JS, Körner A, Kuh D, Kuusisto J, Laakso M, Lin X, Liu Y, Loos RJF, Magnusson PKE, März W, McCarthy MI, Oldehinkel AJ, Ong KK, Pedersen NL, Pereira MA, Peters A, Ridker PM, Sabanayagam C, Sale M, Saleheen D, Saltevo J, Schwarz PE, Sheu WHH, Snieder H, Spector TD, Tabara Y, Tuomilehto J, van Dam RM, Wilson JG, Wilson JF, Wolffenbuttel BHR, Wong TY, Wu JY, Yuan JM, Zonderman AB, Soranzo N, Guo X, Roberts DJ, Florez JC, Sladek R, Dupuis J, Morris AP, Tai ES, Selvin E, Rotter JI, Langenberg C, Barroso I, Meigs JB, EPIC-CVD Consortium; EPIC-InterAct Consortium; Lifelines Cohort Study (2017) Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis. PLoS Med. 14(9):e1002383Google Scholar
  91. Wu L, Cui L, Tam WH, Ma RC, Wang CC (2016) Genetic variants associated with gestational diabetes mellitus: a meta-analysis and subgroup analysis. Sci Rep 29(6):30539Google Scholar
  92. Yan J, Yang HJ (2014) Gestational diabetes mellitus, programing and epigenetics. Matern Fetal Neonatal Med 27(12):1266–1269Google Scholar
  93. Yang M, Peng S, Li W, Wan Z, Fan L, Du Y (2016) Relationships between plasma leptin levels, leptin G2548A, leptin receptor Gln223Arg polymorphisms and gestationaldiabetes mellitus in Chinese population. Sci Rep 6:23948Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Diabetes Center and Transplantation Translational Medicine, Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science and Sichuan Provincial People’s Hospital, School of MedicineUniversity of Electronic Science and Technology of ChinaChengduChina
  2. 2.Department of Medical Genetics and Division of Morbid Genomics, State Key Laboratory of Biotherapy, West China Hospital, West China Medical SchoolSichuan UniversityChengduChina

Personalised recommendations