Genetic Variation in the GCG and in the GLP1R Genes and Antipsychotic-Induced Weight Gain

• Gallini A , DonohueJM, HuskampHA. Diffusion of antipsychotics in the U.S. and French Markets, 1998–2008. Psychiatr. Serv. (2013).
   PubMedGoogle Scholar
• Allison DB , MentoreJL, HeoM et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am. J. Psychiatry 156(11) , 1686–1696 (1999).
   PubMed Web of Science ®Google Scholar
• Lipkovich I , JacobsonJG, CaldwellC, HoffmannVP, KryzhanovskayaL, BeasleyCM. Early predictors of weight gain risk during treatment with olanzapine: analysis of pooled data from 58 clinical trials. Psychopharmacol. Bull.42(4) , 23–39 (2009).
   PubMedGoogle Scholar
• Gebhardt S , HaberhausenM, Heinzel-GutenbrunnerM et al. Antipsychotic-induced body weight gain: predictors and a systematic categorization of the long-term weight course. J. Psychiatr. Res. 43(6) , 620–626 (2009).
   PubMed Web of Science ®Google Scholar
• Lett TA , WallaceTJ, ChowdhuryNI, TiwariAK, KennedyJL, MullerDJ. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol. Psychiatry17(3) , 242–266 (2012).
   PubMed Web of Science ®Google Scholar
• Muller DJ , KennedyJL. Genetics of antipsychotic treatment emergent weight gain in schizophrenia. Pharmacogenomics7(6) , 863–887 (2006).
   PubMed Web of Science ®Google Scholar
• Sicard MN , ZaiCC, TiwariAK et al. Polymorphisms of the HTR2C gene and antipsychotic-induced weight gain: an update and meta-analysis. Pharmacogenomics 11(11) , 1561–1571 (2010).
   PubMed Web of Science ®Google Scholar
• De Luca V , MullerDJ, HwangR et al. HTR2C haplotypes and antipsychotics-induced weight gain: X-linked multimarker analysis. Hum. Psychopharm.22(7) , 463–467 (2007).
   PubMed Web of Science ®Google Scholar
• Brandl EJ , FrydrychowiczC, TiwariAK et al. Association study of polymorphisms in leptin and leptin receptor genes with antipsychotic-induced body weight gain. Prog. Neuropsychopharmacol. Biol. Psychiatry 38(2) , 134–141 (2012).
   PubMed Web of Science ®Google Scholar
• Malhotra AK , CorrellCU, ChowdhuryNI et al. Association between common variants near the melanocortin 4 receptor gene and severe antipsychotic drug-induced weight gain. Arch. Gen. Psychiatr 69(9) , 904–912 (2012).
   PubMed Web of Science ®Google Scholar
• Brandl EJ , TiwariAK, LettTA et al. Exploratory study on association of genetic variation in TBC1D1 with antipsychotic-induced weight gain. Hum. Psychopharmacol. 28(2) , 183–187 (2013).
   PubMed Web of Science ®Google Scholar
• Kieffer TJ , McIntoshCH, PedersonRA. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Endocrinology136(8) , 3585–3596 (1995).
   PubMed Web of Science ®Google Scholar
• Phillips LK , PrinsJB. Update on incretin hormones. Ann. N. Y. Acad. Sci.1243 , E55–74 (2011).
   PubMed Web of Science ®Google Scholar
• Burmeister MA , AyalaJ, DruckerDJ, AyalaJE. Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose. Am. J. Physiol. Endocr. Metab.304(7) , E677–E685 (2013).
   PubMed Web of Science ®Google Scholar
• Poleni PE , Akieda-AsaiS, KodaS et al. Possible involvement of melanocortin-4-receptor and AMP-activated protein kinase in the interaction of glucagon-like peptide-1 and leptin on feeding in rats. Biochem. Biophys. Res. Commun. 420(1) , 36–41 (2012).
   PubMed Web of Science ®Google Scholar
• Fu Z , GilbertER, LiuD. Regulation of insulin synthesis and secretion and pancreatic Beta-cell dysfunction in diabetes. Curr. Diabetes Rev.9(1) , 25–53 (2013).
   PubMedGoogle Scholar
• Herzberg-Schafer S , HeniM, StefanN, HaringHU, FritscheA. Impairment of GLP1-induced insulin secretion: role of genetic background, insulin resistance and hyperglycaemia. Diabetes Obes. Metab.14(Suppl. 3) , 85–90 (2012).
   PubMed Web of Science ®Google Scholar
• Li Y , PerryT, KindyMS et al. GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc. Natl Acad. Sci. USA 106(4) , 1285–1290 (2009).
   PubMed Web of Science ®Google Scholar
• Holscher C . Potential role of glucagon-like peptide-1 (GLP-1) in neuroprotection. CNS Drugs26(10) , 871–882 (2012).
   PubMed Web of Science ®Google Scholar
• Holst JJ , ChristensenM, LundA et al. Regulation of glucagon secretion by incretins. Diabetes Obes. Metab. 13(Suppl. 1) , 89–94 (2011).
   PubMed Web of Science ®Google Scholar
• Dixit TS , SharmaAN, LucotJB, ElasedKM. Antipsychotic-like effect of GLP-1 agonist liraglutide but not DPP-IV inhibitor sitagliptin in mouse model for psychosis. Physiol. Behav.114–115 , 38–41 (2013).
   PubMed Web of Science ®Google Scholar
• Smith GC , VickersMH, ShepherdPR. Olanzapine effects on body composition, food preference, glucose metabolism and insulin sensitivity in the rat. Arch. Physiol. Biochem.117(4), 241–249 (2011).
   PubMedGoogle Scholar
• Smith GC , VickersMH, CognardE, ShepherdPR. Clozapine and quetiapine acutely reduce glucagon-like peptide-1 production and increase glucagon release in obese rats: implications for glucose metabolism and food choice behaviour. Schizophr. Res.115(1) , 30–40 (2009).
   PubMed Web of Science ®Google Scholar
• van der Zwaal EM , MerkesteinM, LamYK et al. The acute effects of olanzapine on ghrelin secretion, CCK sensitivity, meal size, locomotor activity and body temperature. Int. J. Obes. (Lond.) 36(2) , 254–261 (2012).
   PubMed Web of Science ®Google Scholar
• Vidarsdottir S , RoelfsemaF, StreeflandT, HolstJJ, RehfeldJF, PijlH. Short-term treatment with olanzapine does not modulate gut hormone secretion: olanzapine disintegrating versus standard tablets. Eur. J. Endocrinol.162(1) , 75–83 (2010).
   PubMed Web of Science ®Google Scholar
• Lykkegaard K , LarsenPJ, VrangN, BockC, BockT, KnudsenLB. The once-daily human GLP-1 analog, liraglutide, reduces olanzapine-induced weight gain and glucose intolerance. Schizophr. Res.103(1–3) , 94–103 (2008).
   PubMed Web of Science ®Google Scholar
• Flint A , KapitzaC, ZdravkovicM. The once-daily human GLP-1 analogue liraglutide impacts appetite and energy intake in patients with Type 2 diabetes after short-term treatment. Diabetes Obes. Metab.15(10) , 958–962 (2013).
   PubMed Web of Science ®Google Scholar
• Vilsboll T , ChristensenM, JunkerAE, KnopFK, GluudLL. Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials. BMJ344 , d7771 (2012).
   PubMed Web of Science ®Google Scholar
• Astrup A , CarraroR, FinerN et al. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int. J. Obes. (Lond.) 36(6) , 843–854 (2012).
   PubMed Web of Science ®Google Scholar
• Ebdrup BH , KnopFK, IshoyPL et al. Glucagon-like peptide-1 analogs against antipsychotic-induced weight gain: potential physiological benefits. BMC Med. 10 , 92 (2012).
   PubMed Web of Science ®Google Scholar
• Torekov SS , MaL, GrarupN et al. Homozygous carriers of the G allele of rs4664447 of the glucagon gene (GCG) are characterised by decreased fasting and stimulated levels of insulin, glucagon and glucagon-like peptide (GLP)-1. Diabetologia 54(11) , 2820–2831 (2011).
   PubMed Web of Science ®Google Scholar
• Sheikh HI , DoughertyLR, HaydenEP, KleinDN, SinghSM. Glucagon-like peptide-1 receptor gene polymorphism (Leu260Phe) is associated with morning cortisol in preschoolers. Prog. Neuropsychopharmacol. Biol. Psychiatry34(6) , 980–983 (2010).
   PubMed Web of Science ®Google Scholar
• Sathananthan A , ManCD, MichelettoF et al. Common genetic variation in GLP1R and insulin secretion in response to exogenous GLP-1 in nondiabetic subjects: a pilot study. Diabetes Care 33(9) , 2074–2076 (2010).
   PubMed Web of Science ®Google Scholar
• Kumar KG , PooleAC, YorkB, VolaufovaJ, ZuberiA, RichardsBK. Quantitative trait loci for carbohydrate and total energy intake on mouse chromosome 17: congenic strain confirmation and candidate gene analyses (Glo1, Glp1r). Am. J. Physiol. Regul. Integr. Comp. Physiol.292(1) , R207–R216 (2007).
   PubMed Web of Science ®Google Scholar
• Kumar KG , ByerleyLO, VolaufovaJ et al. Genetic variation in Glp1r expression influences the rate of gastric emptying in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294(2) , R362–R371 (2008).
   PubMed Web of Science ®Google Scholar
• Scrocchi LA , BrownTJ, MacluskyN et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat. Med. 2(11) , 1254–1258 (1996).
   PubMed Web of Science ®Google Scholar
• Tiwari AK , RodgersJB, SicardM et al. Association study of polymorphisms in cholecystokinin gene and its receptors with antipsychotic induced weight gain in schizophrenia patients. Prog. Neuropsychopharmacol. Biol. Psychiatry 34(8) , 1484–1490 (2010).
   PubMed Web of Science ®Google Scholar
• Tiwari AK , ZaiCC, LikhodiO et al. A common polymorphism in the cannabinoid receptor 1 (CNR1) gene is associated with antipsychotic-induced weight gain in schizophrenia. Neuropsychopharmacology 35(6) , 1315–1324 (2010).
   PubMed Web of Science ®Google Scholar
• Tiwari AK , BrandlEJ, WeberC et al. Association of a functional polymorphism in neuropeptide Y with antipsychotic-induced weight gain in schizophrenia patients. J. Clin. Psychopharmacol. 33(1) , 11–17 (2013).
   PubMed Web of Science ®Google Scholar
• Lahiri DK , NurnbergerJI Jr. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res.19(19) , 5444 (1991).
   PubMed Web of Science ®Google Scholar
• Barrett JC , FryB, MallerJ, DalyMJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics21(2) , 263–265 (2005).
   PubMed Web of Science ®Google Scholar
• Dudbridge F . Pedigree disequilibrium tests for multilocus haplotypes. Genet. Epidemiol.25(2) , 115–121 (2003).
   PubMed Web of Science ®Google Scholar
• Calle ML , UrreaV, MalatsN, van Steen K. mbmdr: an R package for exploring gene–gene interactions associated with binary or quantitative traits. Bioinformatics26(17) , 2198–2199 (2010).
   PubMed Web of Science ®Google Scholar
• Nyholt DR . A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Hum. Genet.74(4) , 765–769 (2004).
   PubMed Web of Science ®Google Scholar
• Carlborg O , HaleyCS. Epistasis: too often neglected in complex trait studies? Nat. Rev. Genet.5(8) , 618–625 (2004).
   PubMed Web of Science ®Google Scholar
• Dunham I , KundajeA, AldredSF et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489(7414) , 57–74 (2012).
   PubMed Web of Science ®Google Scholar
• Stephan M , RadickeA, LeutloffS et al. Dipeptidyl peptidase IV (DPP4)-deficiency attenuates diet-induced obesity in rats: possible implications for the hypothalamic neuropeptidergic system. Behav. Brain Res. 216(2) , 712–718 (2011).
   PubMed Web of Science ®Google Scholar
• Yagi T , NishiS, HinataS, MurakamiM, YoshimiT. A population association study of four candidate genes (hexokinase II, glucagon-like peptide-1 receptor, fatty acid binding protein-2, and apolipoprotein C-II) with Type 2 diabetes and impaired glucose tolerance in Japanese subjects. Diabet. Med.13(10) , 902–907 (1996).
   PubMed Web of Science ®Google Scholar
• Laukkanen O , LindstromJ, ErikssonJ et al. Polymorphisms in the SLC2A2 (GLUT2) gene are associated with the conversion from impaired glucose tolerance to Type 2 diabetes: the Finnish diabetes prevention study. Diabetes 54(7) , 2256–2260 (2005).
   PubMed Web of Science ®Google Scholar

▪ Websites

• Exenatide for the treatment of weight gain associated with olanzapine in obese adults. http://clinicaltrials.gov/ct2/show/NCT00845507
   Google Scholar
• International HapMap Project. http://hapmap.ncbi.nlm.nih.gov
   Google Scholar
• Gauderman WJ, Morrison JM. A computer program for power and sample size calculations for genetic-epidemiology studies (2006). http://hydra.usc.edu/gxe
   Google Scholar