Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge.
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- Saxena, Richa; Hivert, Marie-France; Langenberg, Claudia; Tanaka, Toshiko; Pankow, James S; Vollenweider, Peter; Lyssenko, Valeriya; Bouatia-Naji, Nabila; Dupuis, JosΓ©e; Jackson, Anne U; Kao, W H Linda; Li, Man; Glazer, Nicole L; Manning, Alisa K; Luan, Jian'an; Stringham, Heather M; Prokopenko, Inga; Johnson, Toby; Grarup, Niels; Boesgaard, Trine W; Lecoeur, CΓ©cile; Shrader, Peter; O'Connell, Jeffrey; Ingelsson, Erik; Couper, David J; Rice, Kenneth; Song, Kijoung; Andreasen, Camilla H; Dina, Christian; KΓΆttgen, Anna; Le Bacquer, Olivier; Pattou, FranΓ§ois; Taneera, Jalal; Steinthorsdottir, Valgerdur; Rybin, Denis; Ardlie, Kristin; Sampson, Michael; Qi, Lu; van Hoek, Mandy; Weedon, Michael N; Aulchenko, Yurii S; Voight, Benjamin F; Grallert, Harald; Balkau, Beverley; Bergman, Richard N; Bielinski, Suzette J; Bonnefond, Amelie; Bonnycastle, Lori L; Borch-Johnsen, Knut; BΓΆttcher, Yvonne; Brunner, Eric; Buchanan, Thomas A; Bumpstead, Suzannah J; Cavalcanti-ProenΓ§a, Christine; Charpentier, Guillaume; Chen, Yii-Der Ida; Chines, Peter S; Collins, Francis S; Cornelis, Marilyn; J Crawford, Gabriel; Delplanque, Jerome; Doney, Alex; Egan, Josephine M; Erdos, Michael R; Firmann, Mathieu; Forouhi, Nita G; Fox, Caroline S; Goodarzi, Mark O; Graessler, JΓΌrgen; Hingorani, Aroon; Isomaa, Bo; JΓΈrgensen, Torben; Kivimaki, Mika; Kovacs, Peter; Krohn, Knut; Kumari, Meena; Lauritzen, Torsten; LΓ©vy-Marchal, Claire; Mayor, Vladimir; McAteer, Jarred B; Meyre, David; Mitchell, Braxton D; Mohlke, Karen L; Morken, Mario A; Narisu, Narisu; Palmer, Colin N A; Pakyz, Ruth; Pascoe, Laura; Payne, Felicity; Pearson, Daniel; Rathmann, Wolfgang; Sandbaek, Annelli; Sayer, Avan Aihie; Scott, Laura J; Sharp, Stephen J; Sijbrands, Eric; Singleton, Andrew; Siscovick, David S; Smith, Nicholas L; SparsΓΈ, Thomas; Swift, Amy J; Syddall, Holly; Thorleifsson, Gudmar; TΓΆnjes, Anke; Tuomi, Tiinamaija; Tuomilehto, Jaakko; Valle, Timo T; Waeber, GΓ©rard; Walley, Andrew; Waterworth, Dawn M; Zeggini, Eleftheria; Zhao, Jing Hua; GIANT consortium; MAGIC investigators; Illig, Thomas; Wichmann, H Erich; Wilson, James F; van Duijn, Cornelia; Hu, Frank B; Morris, Andrew D; Frayling, Timothy M; Hattersley, Andrew T; Thorsteinsdottir, Unnur; Stefansson, Kari; Nilsson, Peter; SyvΓ€nen, Ann-Christine; Shuldiner, Alan R; Walker, Mark; Bornstein, Stefan R; Schwarz, Peter; Williams, Gordon H; Nathan, David M; Kuusisto, Johanna; Laakso, Markku; Cooper, Cyrus; Marmot, Michael; Ferrucci, Luigi; Mooser, Vincent; Stumvoll, Michael; Loos, Ruth J F; Altshuler, David; Psaty, Bruce M; Rotter, Jerome I; Boerwinkle, Eric; Hansen, Torben; Pedersen, Oluf; Florez, Jose C; McCarthy, Mark I; Boehnke, Michael; Barroso, InΓͺs; Sladek, Robert; Froguel, Philippe; Meigs, James B; Groop, Leif; Wareham, Nicholas J; Watanabe, Richard M
- Year
- 2010
- Journal
- Nature genetics
- PMID
- 20081857
- DOI
- 10.1038/ng.521
- PMCID
- PMC2922003
Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2-h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).
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| Expression-based genome-wide association study links the receptor CD44 in adipose tissue with type 2 diabetes. | Kodama K et al. | β | 2012 | β |
| Finding genes and variants for lipid levels after genome-wide association analysis. | Willer CJ et al. | β | 2012 | β |
| Five years of GWAS discovery. | Visscher PM et al. | β | 2012 | β |
| From genotype to human Ξ² cell phenotype and beyond. | Marchetti P et al. | β | 2012 | β |
| Gene-environment interactions in the development of type 2 diabetes: recent progress and continuing challenges. | Cornelis MC et al. | β | 2012 | β |
| Genetic advances of type 2 diabetes in Chinese populations. | Yu W et al. | β | 2012 | β |
| Genetic origins of low birth weight. | Yaghootkar H et al. | β | 2012 | β |
| Genetic risk factors for type 2 diabetes: a trans-regulatory genetic architecture? | Elbein SC et al. | β | 2012 | β |
| Glucagon-like peptide-1 and its cardiovascular effects. | Heo KS et al. | β | 2012 | β |
| Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. | StancΓ‘kovΓ‘ A et al. | β | 2012 | β |
| Identification of novel type 2 diabetes candidate genes involved in the crosstalk between the mitochondrial and the insulin signaling systems. | Mercader JM et al. | β | 2012 | β |
| Impact of common variation in bone-related genes on type 2 diabetes and related traits. | Billings LK et al. | β | 2012 | β |
| Improved insulin sensitivity after treatment with PPARΞ³ and PPARΞ± ligands is mediated by genetically modulated transcripts. | Rasouli N et al. | β | 2012 | β |
| Individualized therapy for type 2 diabetes: clinical implications of pharmacogenetic data. | Mannino GC et al. | β | 2012 | β |
| Interactions between genetic background, insulin resistance and Ξ²-cell function. | Kahn SE et al. | β | 2012 | β |
| Is FTO a type 2 diabetes susceptibility gene? | Meyre D | β | 2012 | β |
| Laparoscopic ileal interposition with diverted sleeve gastrectomy for treatment of type 2 diabetes. | Kota SK et al. | β | 2012 | β |
| Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. | Scott RA et al. | β | 2012 | β |
| Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. | Morris AP et al. | β | 2012 | β |
| Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci. | Saxena R et al. | β | 2012 | β |
| Menin and GIP are inversely regulated by food intake and diet via PI3/AKT signaling in the proximal duodenum. | Angevine KR et al. | β | 2012 | β |
| No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels. | Scott RA et al. | β | 2012 | β |
| Pancreatic beta-cell function and type 2 diabetes risk: quantify the causal effect using a Mendelian randomization approach based on meta-analyses. | Song Y et al. | β | 2012 | β |
| Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases. | Perry JR et al. | β | 2012 | β |
| Targeting the glucagon receptor family for diabetes and obesity therapy. | Cho YM et al. | β | 2012 | β |
| The metabochip, a custom genotyping array for genetic studies of metabolic, cardiovascular, and anthropometric traits. | Voight BF et al. | β | 2012 | β |
| The role of inflammatory pathway genetic variation on maternal metabolic phenotypes during pregnancy. | Urbanek M et al. | β | 2012 | β |
| This I believe: gaining new insights through integrating "old" data. | Loos RJ et al. | β | 2012 | β |
| Transcription factor-7-like 2 gene variants are strongly associated with type 2 diabetes in Lebanese subjects. | Nemr R et al. | β | 2012 | β |
| Weight-loss diets modify glucose-dependent insulinotropic polypeptide receptor rs2287019 genotype effects on changes in body weight, fasting glucose, and insulin resistance: the Preventing Overweight Using Novel Dietary Strategies trial. | Qi Q et al. | β | 2012 | β |
| Who should we target for diabetes prevention and diabetes risk reduction? | BlΓΌher S et al. | β | 2012 | β |
| Adaptive selection of an incretin gene in Eurasian populations. | Chang CL et al. | β | 2011 | β |
| Adenylyl cyclase 8 is central to glucagon-like peptide 1 signalling and effects of chronically elevated glucose in rat and human pancreatic beta cells. | Roger B et al. | β | 2011 | β |
| A gene-centric association scan for Coagulation Factor VII levels in European and African Americans: the Candidate Gene Association Resource (CARe) Consortium. | Taylor KC et al. | β | 2011 | β |
| A genome-wide association study confirms previously reported loci for type 2 diabetes in Han Chinese. | Cui B et al. | β | 2011 | β |
| AKT1 polymorphisms are associated with risk for metabolic syndrome. | Devaney JM et al. | β | 2011 | β |
| A role for coding functional variants in HNF4A in type 2 diabetes susceptibility. | Jafar-Mohammadi B et al. | β | 2011 | β |
| Association of new loci identified in European genome-wide association studies with susceptibility to type 2 diabetes in the Japanese. | Ohshige T et al. | β | 2011 | β |
| Associations of common genetic variants with age-related changes in fasting and postload glucose: evidence from 18 years of follow-up of the Whitehall II cohort. | Jensen AC et al. | β | 2011 | β |
| Association study of type 2 diabetes genetic susceptibility variants and risk of pancreatic cancer: an analysis of PanScan-I data. | Pierce BL et al. | β | 2011 | β |
| Developments in obesity genetics in the era of genome-wide association studies. | Day FR et al. | β | 2011 | β |
| Effects of 34 risk loci for type 2 diabetes or hyperglycemia on lipoprotein subclasses and their composition in 6,580 nondiabetic Finnish men. | StanΔΓ‘kovΓ‘ A et al. | β | 2011 | β |
| Effects of genetic variants in ADCY5, GIPR, GCKR and VPS13C on early impairment of glucose and insulin metabolism in children. | Windholz J et al. | β | 2011 | β |
| Emerging applications of metabolomic and genomic profiling in diabetic clinical medicine. | McKillop AM et al. | β | 2011 | β |
| GCKR mutations in Japanese families with clustered type 2 diabetes. | Tanaka D et al. | β | 2011 | β |
| Genetic associations with metabolic syndrome and its quantitative traits by race/ethnicity in the United States. | Vassy JL et al. | β | 2011 | β |
| Genetic determinants of plasma triglycerides. | Johansen CT et al. | β | 2011 | β |
| Genetic determinants of variability in glycated hemoglobin (HbA(1c)) in humans: review of recent progress and prospects for use in diabetes care. | Soranzo N | β | 2011 | β |
| Genetic predisposition to long-term nondiabetic deteriorations in glucose homeostasis: Ten-year follow-up of the GLACIER study. | RenstrΓΆm F et al. | β | 2011 | β |
| Genetics of type 2 diabetes: pathophysiologic and clinical relevance. | Herder C et al. | β | 2011 | β |
| Genetics of type 2 diabetes: the GWAS era and future perspectives [Review]. | Imamura M et al. | β | 2011 | β |
| Genetic variation within the NR1H2 gene encoding liver X receptor Ξ² associates with insulin secretion in subjects at increased risk for type 2 diabetes. | Ketterer C et al. | β | 2011 | β |
| Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes. | Ketterer C et al. | β | 2011 | β |
| Genomewide analysis of inherited variation associated with phosphorylation of PI3K/AKT/mTOR signaling proteins. | Hutz JE et al. | β | 2011 | β |
| Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes. | Strawbridge RJ et al. | β | 2011 | β |
| Genome-wide association studies and type 2 diabetes. | Wheeler E et al. | β | 2011 | β |
| Identification of metabolic modifiers that underlie phenotypic variations in energy-balance regulation. | Chang CL et al. | β | 2011 | β |
| Inherited destiny? Genetics and gestational diabetes mellitus. | Watanabe RM | β | 2011 | β |
| Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. | Kim YJ et al. | β | 2011 | β |
| Loss of incretin effect is a specific, important, and early characteristic of type 2 diabetes. | Holst JJ et al. | β | 2011 | β |
| Metabolic characterization of volume overload heart failure due to aorto-caval fistula in rats. | Melenovsky V et al. | β | 2011 | β |
| New type 2 diabetes risk genes provide new insights in insulin secretion mechanisms. | SchΓ€fer SA et al. | β | 2011 | β |
| Plasma gastric inhibitory polypeptide and glucagon-like peptide-1 levels after glucose loading are associated with different factors in Japanese subjects. | Harada N et al. | β | 2011 | β |
| Pleiotropic effects of GIP on islet function involve osteopontin. | Lyssenko V et al. | β | 2011 | β |
| PWD/PhJ and WSB/EiJ mice are resistant to diet-induced obesity but have abnormal insulin secretion. | Lee KT et al. | β | 2011 | β |
| T2DM: Why Epigenetics? | Fradin D et al. | β | 2011 | β |
| The diabetogenic VPS13C/C2CD4A/C2CD4B rs7172432 variant impairs glucose-stimulated insulin response in 5,722 non-diabetic Danish individuals. | Grarup N et al. | β | 2011 | β |
| The heritability of beta cell function parameters in a mixed meal test design. | Simonis-Bik AM et al. | β | 2011 | β |
| The Lin28/let-7 axis regulates glucose metabolism. | Zhu H et al. | β | 2011 | β |
| Two incretin hormones GLP-1 and GIP: comparison of their actions in insulin secretion and Ξ² cell preservation. | Yabe D et al. | β | 2011 | β |
| Type 2 diabetes across generations: from pathophysiology to prevention and management. | Nolan CJ et al. | β | 2011 | β |
| Updated genetic score based on 34 confirmed type 2 diabetes Loci is associated with diabetes incidence and regression to normoglycemia in the diabetes prevention program. | Hivert MF et al. | β | 2011 | β |
| Update on incretin hormones. | Phillips LK et al. | β | 2011 | β |
| Use of mouse models in studying type 2 diabetes mellitus. | Lee AW et al. | β | 2011 | β |
| A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. | Yamauchi T et al. | β | 2010 | β |
| Analyses and comparison of imputation-based association methods. | Pei YF et al. | β | 2010 | β |
| A new statistic to evaluate imputation reliability. | Lin P et al. | β | 2010 | β |
| Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. | Speliotes EK et al. | β | 2010 | β |
| Association of rs780094 in GCKR with metabolic traits and incident diabetes and cardiovascular disease: the ARIC Study. | Bi M et al. | β | 2010 | β |
| Combined effects of 19 common variations on type 2 diabetes in Chinese: results from two community-based studies. | Xu M et al. | β | 2010 | β |
| Common inherited variation in mitochondrial genes is not enriched for associations with type 2 diabetes or related glycemic traits. | SegrΓ¨ AV et al. | β | 2010 | β |
| Common variants at 10 genomic loci influence hemoglobin Aβ(C) levels via glycemic and nonglycemic pathways. | Soranzo N et al. | β | 2010 | β |
| Defects in insulin secretion and action in the pathogenesis of type 2 diabetes mellitus. | Tripathy D et al. | β | 2010 | β |
| Detailed physiologic characterization reveals diverse mechanisms for novel genetic Loci regulating glucose and insulin metabolism in humans. | Ingelsson E et al. | β | 2010 | β |
| Epidemiology of type 2 diabetes and cardiovascular disease: translation from population to prevention: the Kelly West award lecture 2009. | Meigs JB | β | 2010 | β |
| Evaluation of the association between the AC3 genetic polymorphisms and obesity in a Chinese Han population. | Wang H et al. | β | 2010 | β |
| From genetic association to molecular mechanism. | van de Bunt M et al. | β | 2010 | β |
| Genetics of atherothrombosis and thrombophilia. | MΓ€larstig A et al. | β | 2010 | β |
| Genetics of type 2 diabetes. | Smushkin G et al. | β | 2010 | β |
| Genetic variants affecting incretin sensitivity and incretin secretion. | MΓΌssig K et al. | β | 2010 | β |
| Genome-wide association studies and large-scale collaborations in epidemiology. | Psaty BM et al. | β | 2010 | β |
| GIP and GLP-1, the two incretin hormones: Similarities and differences. | Seino Y et al. | β | 2010 | β |
| GIP: no longer the neglected incretin twin? | Kulkarni RN | β | 2010 | β |
| Glucose intolerance and reduced proliferation of pancreatic beta-cells in transgenic pigs with impaired glucose-dependent insulinotropic polypeptide function. | Renner S et al. | β | 2010 | β |
| 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. | Freathy RM et al. | β | 2010 | β |
| Inborn variation in metabolism. | Mootha VK et al. | β | 2010 | β |
| K-cells and glucose-dependent insulinotropic polypeptide in health and disease. | Cho YM et al. | β | 2010 | β |
| Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. | Heid IM et al. | β | 2010 | β |
| Neural plasticity, human genetics, and risk for alcohol dependence. | Hill SY | β | 2010 | β |
| New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. | Dupuis J et al. | β | 2010 | β |
| Pharmacogenetics of Anti-Diabetes Drugs. | Distefano JK et al. | β | 2010 | β |
| Physiologic characterization of type 2 diabetes-related loci. | Grarup N et al. | β | 2010 | β |
| Research highlights from the latest articles in diabetes research. | Reitman ML | β | 2010 | β |
| The emerging genetics of type 2 diabetes. | Bonnefond A et al. | β | 2010 | β |
| The genetics of insulin resistance: Where's Waldo? | Watanabe RM | β | 2010 | β |
| The genetics of type 2 diabetes: what have we learned from GWAS? | Billings LK et al. | β | 2010 | β |
| The Incretins and Pancreatic beta-Cells: Use of Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide to Cure Type 2 Diabetes Mellitus. | Kim MH et al. | β | 2010 | β |
| The TCF7L2 diabetes risk variant is associated with HbAβ(C) levels: a genome-wide association meta-analysis. | Franklin CS et al. | β | 2010 | β |
| Transgenic pigs as models for translational biomedical research. | Aigner B et al. | β | 2010 | β |
| Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. | Voight BF et al. | β | 2010 | β |
| Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight. | Andersson EA et al. | β | 2010 | β |
| Variants at DGKB/TMEM195, ADRA2A, GLIS3 and C2CD4B loci are associated with reduced glucose-stimulated beta cell function in middle-aged Danish people. | Boesgaard TW et al. | β | 2010 | β |
| Variants from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 are associated with glucose metabolism in the Chinese. | Hu C et al. | β | 2010 | β |