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Association between DPYSL2 gene polymorphisms and alcohol dependence in Caucasian samples

  • Psychiatry and Preclinical Psychiatric Studies - Original Article
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Abstract

The DPYSL2 gene at 8p22-p21 is expressed widely in neuronal tissues and has been implicated in multiple psychiatric disorders such as Alzheimer’s disease and schizophrenia. We therefore hypothesized that DPYSL2 gene polymorphisms may play a role in alcohol dependence (AD). We investigated the genetic associations of 57 single-nucleotide polymorphisms (SNPs) within the DPYSL2 gene with AD using two Caucasian samples—the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls), and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). The SNP rs11995227 was most significantly associated with AD (p = 0.000122) in the COGA sample while one flanking SNP rs7832576 revealed the second most significant association with AD (p = 0.00163) in the COGA sample and association with AD (p = 0.0195) in the SAGE sample. Meta-analysis of two samples showed both rs119952227 and rs7832576 were associated with AD (p = 0.000363 and 0.000184, respectively). Furthermore, the C-A haplotype from rs11995227 and rs7832576 revealed significant association with AD (p = 0.0000899) in the COGA sample while the T-G haplotype revealed association with AD both in the COGA and SAGE samples (p = 0.00098 and 0.021, respectively). These findings suggest that genetic variants in DPYSL2 may play a role in susceptibility to AD.

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References

  • Baron M, Gomez-Tortosa E, Bochdanovits Z, Gobernado I, Rabano A, Munoz DG, Heutink P, Jimenez-Escrig A (2012) Extended kindred with recessive late-onset Alzheimer disease maps to locus 8p22-p21.2: a genome-wide linkage analysis. Alzheimer Dis Assoc Disord 26:91–95

    Article  PubMed  Google Scholar 

  • Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265

    Article  CAS  PubMed  Google Scholar 

  • Bierut LJ, Agrawal A, Bucholz KK, Doheny KF, Laurie C, Pugh E, Fisher S, Fox L, Howells W, Bertelsen S, Hinrichs AL, Almasy L, Breslau N, Culverhouse RC, Dick DM, Edenberg HJ, Foroud T, Grucza RA, Hatsukami D, Hesselbrock V, Johnson EO, Kramer J, Krueger RF, Kuperman S, Lynskey M, Mann K, Neuman RJ, Nothen MM, Nurnberger JI Jr, Porjesz B, Ridinger M, Saccone NL, Saccone SF, Schuckit MA, Tischfield JA, Wang JC, Rietschel M, Goate AM, Rice JP (2010) A genome-wide association study of alcohol dependence. Proc Natl Acad Sci USA 107:5082–5087

    Article  CAS  PubMed  Google Scholar 

  • Boffetta P, Hashibe M (2006) Alcohol and cancer. Lancet Oncol 7:149–156

    Article  CAS  PubMed  Google Scholar 

  • Brittain JM, Duarte DB, Wilson SM, Zhu W, Ballard C, Johnson PL, Liu N, Xiong W, Ripsch MS, Wang Y, Fehrenbacher JC, Fitz SD, Khanna M, Park CK, Schmutzler BS, Cheon BM, Due MR, Brustovetsky T, Ashpole NM, Hudmon A, Meroueh SO, Hingtgen CM, Brustovetsky N, Ji R, Hurley JH, Jin X, Shekhar A, Xu X, Oxford GS, Vasko MR, White FA, Khanna R (2011) Suppression of inflammatory and neuropathic pain by uncoupling CRMP-2 from the presynaptic Ca(2+) channel complex. Nature Med 17:822–829

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Campbell KE, Zobeck TS, Bertolucci D (1995) Trends in alcohol-related fatal traffic crashes. NIAAA Surveillance Report #34, Maryland, pp 1977–1993

    Google Scholar 

  • Christie TL, Starovic-Subota O, Childs S (2006) Zebrafish collapsin response mediator protein (CRMP)-2 is expressed in developing neurons. Gene Expr Patterns 6(2):193–200

    Article  CAS  PubMed  Google Scholar 

  • Cloninger CR, Van Eerdewegh P, Goate A, Edenberg HJ, Blangero J, Hesselbrock V, Reich T, Nurnberger JJr, Schuckit M, Porjesz B, Crowe R, Rice JP, Foroud T, Przybeck TR, Almasy L, Bucholz K, Wu W, Shears S, Carr K, Crose C, Willig C, Zhao J, Tischfield JA, Li TK, Conneally PM, Begleiter H (1998) Anxiety proneness linked to epistatic loci in genome scan of human personality traits. Am J Med Genet 81:313–317

    Article  CAS  PubMed  Google Scholar 

  • Druesne-Pecollo N, Tehard B, Mallet Y, Gerber M, Norat T, Hercberg S, Latino-Martel P (2009) Alcohol and genetic polymorphisms: effect on risk of alcohol-related cancer. Lancet Oncol 10:173–180

    Article  CAS  PubMed  Google Scholar 

  • Ducci F, Goldman D (2008) Genetic approaches to addiction: genes and alcohol. Addiction 103:1414–1428

    Article  PubMed Central  PubMed  Google Scholar 

  • Dudbridge F (2008) Likelihood-based association analysis for nuclear families and unrelated subjects with missing genotype data. Hum Hered 66:87–98

    Article  PubMed Central  PubMed  Google Scholar 

  • Edenberg HJ, Koller DL, Xuei X, Wetherill L, McClintick JN, Almasy L, Bierut LJ, Bucholz KK, Goate A, Aliev F, Dick D, Hesselbrock V, Hinrichs A, Kramer J, Kuperman S, Nurnberger JI Jr, Rice JP, Schuckit MA, Taylor R, Todd Webb B, Tischfield JA, Porjesz B, Foroud T (2010) Genome-wide association study of alcohol dependence implicates a region on chromosome 11. Alcohol: Clin Exp Res 34:840–852

    CAS  Google Scholar 

  • Fallin MD, Lasseter VK, Liu Y, Avramopoulos D, McGrath J, Wolyniec PS, Nestadt G, Liang KY, Chen PL, Valle D, Pulver AE (2011) Linkage and association on 8p21.2-p21.1 in schizophrenia. Am J Med Genet B Neuropsychiatr Genet 156:188–197

    Article  CAS  PubMed  Google Scholar 

  • Fukata Y, Itoh TJ, Kimura T, Menager C, Nishimura T, Shiromizu T, Watanabe H, Inagaki N, Iwamatsu A, Hotani H, Kaibuchi K (2002) CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nature Cell Biol 4:583–591

    CAS  PubMed  Google Scholar 

  • Gelernter J, Kranzler HR (2009) Genetics of alcohol dependence. Hum Genet 126:91–99

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gordis E, Tabakoff B, Goldman D, Berg K (1990) Finding the gene(s) for alcoholism. J Am Med Assoc 263:2094–2095

    Article  CAS  Google Scholar 

  • Goshima Y, Nakamura F, Strittmatter P, Strittmatter SM (1995) Collapsin-induced growth cone collapse mediated by an intracellular protein related to UNC-33. Nature 376(6540):509–514

    Article  CAS  PubMed  Google Scholar 

  • Grant BF, Stinson FS, Dawson DA, Chou SP, Dufour MC, Compton W, Pickering RP, Kaplan K (2004a) Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders: results from the National epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 61:807–816

    Article  PubMed  Google Scholar 

  • Grant BF, Stinson FS, Dawson DA, Chou SP, Ruan WJ, Pickering RP (2004b) Co-occurrence of 12-month alcohol and drug use disorders and personality disorders in the United States: results from the national epidemiologic survey on alcohol and related conditions. Arch Gen Psychiatry 61:361–368

    Article  PubMed  Google Scholar 

  • Hamajima N, Matsuda K, Sakata S, Tamaki N, Sasaki M, Nonaka M (1996) A novel gene family defined by human dihydropyrimidinase and three related proteins with differential tissue distribution. Gene 180:157–163

    Article  CAS  PubMed  Google Scholar 

  • Heath AC, Bucholz KK, Madden PA, Dinwiddie SH, Slutske WS, Bierut LJ, Statham DJ, Dunne MP, Whitfield JB, Martin NG (1997) Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychol Med 27:1381–1396

    Article  CAS  PubMed  Google Scholar 

  • Kékesi KA, Juhász G, Simor A, Gulyássy P, Szegő EM, Hunyadi-Gulyás E, Darula Z, Medzihradszky KF, Palkovits M, Penke B, Czurkó A (2012) Altered functional protein networks in the prefrontal cortex and amygdala of victims of suicide. PLoS One 7(12):e50532

    Article  PubMed Central  PubMed  Google Scholar 

  • Kendler KS, Heath AC, Neale MC, Kessler RC, Eaves LJ (1992) A population-based twin study of alcoholism in women. JAMA: J Am Med Assoc 268:1877–1882

    Article  CAS  Google Scholar 

  • Kendler KS, Myers JM, O’Neill FA, Martin R, Murphy B, MacLean CJ, Walsh D, Straub RE (2000) Clinical features of schizophrenia and linkage to chromosomes 5q, 6p, 8p, and 10p in the Irish Study of High-Density Schizophrenia Families. Am J Psychiatry 157:402–408

    Article  CAS  PubMed  Google Scholar 

  • Khanna R, Wilson SM, Brittain JM, Weimer J, Sultana R, Butterfield A, Hensley K (2012) Opening Pandora’s jar: a primer on the putative roles of CRMP2 in a panoply of neurodegenerative, sensory and motor neuron, and central disorders. Future Neurol 7(6):749–771

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Koide T, Aleksic B, Ito Y, Usui H, Yoshimi A, Inada T, Suzuki M, Hashimoto R, Takeda M, Iwata N, Ozaki N (2010) A two-stage case-control association study of the dihydropyrimidinase-like 2 gene (DPYSL2) with schizophrenia in Japanese subjects. J Hum Genet 55:469–472

    Article  CAS  PubMed  Google Scholar 

  • Lind PA, Macgregor S, Vink JM, Pergadia ML, Hansell NK, de Moor MH, Smit AB, Hottenga JJ, Richter MM, Heath AC, Martin NG, Willemsen G, de Geus EJ, Vogelzangs N, Penninx BW, Whitfield JB, Montgomery GW, Boomsma DI, Madden PA (2010) A genomewide association study of nicotine and alcohol dependence in Australian and Dutch populations. Twin Res Hum Gen 13:10–29

    Google Scholar 

  • Longnecker MP (1995) Alcohol consumption and risk of cancer in humans: an overview. Alcohol 12:87–96

    Article  CAS  PubMed  Google Scholar 

  • Maier C, Herkommer K, Hoegel J, Vogel W, Paissm T (2005) A genomewide linkage analysis for prostate cancer susceptibility genes in families from Germany. Eur J Hum Genet 13:352–360

    Article  CAS  PubMed  Google Scholar 

  • Mayfield RD, Harris RA, Schuckit MA (2008) Genetic factors influencing alcohol dependence. Br J Pharmacol 154:275–287

    Article  CAS  PubMed  Google Scholar 

  • Nakata K, Ujike H, Sakai A, Takaki M, Imamura T, Tanaka Y, Kuroda S (2003) The human dihydropyrimidinase-related protein 2 gene on chromosome 8p21 is associated with paranoid-type schizophrenia. Biol Psychiatry 53:571–576

    Article  CAS  PubMed  Google Scholar 

  • Park N, Juo SH, Cheng R, Liu J, Loth JE, Lilliston B, Nee J, Grunn A, Kanyas K, Lerer B, Endicott J, Gilliam TC, Baron M (2004) Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia. Mol Psychiatry 9:1091–1099

    Article  CAS  PubMed  Google Scholar 

  • Prescott CA, Kendler KS (1999) Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. Am J Psychiatry 156:34–40

    CAS  PubMed  Google Scholar 

  • Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender DS, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Amer J Hum Genet 3:559–575

    Article  Google Scholar 

  • Tabarés-Seisdedos R, Rubenstein JL (2009) Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer. Mol Psychiatry 14:563–589

    Article  PubMed  Google Scholar 

  • Vincent P, Collette Y, Marignier R, Vuaillat C, Rogemond V, Davoust N, Malcus C, Cavagna S, Gessain A, Machuca-Gayet I, Belin M-F, Quach T, Giraudon P (2005) A role for the neuronal protein collapsin response mediator protein 2 in T lymphocyte polarization and migration. J Immun 175:7650–7660

    CAS  PubMed  Google Scholar 

  • Wang KS, Liu XF, Zhang QY, Pan Y, Aragam N, Zeng M (2011) Meta-analysis of two genome-wide association studies identifies 3 new loci for alcohol dependence. J Psychiatr Res 45:1419–1425

    Article  PubMed  Google Scholar 

  • Williamson R, van Aalten L, Mann DM, Platt B, Plattner F, Bedford L, Mayer J, Howlett D, Usardi A, Sutherland C, Cole AR (2011) CRMP2 Hyperphosphorylation is Characteristic of Alzheimer’s Disease and not a Feature Common to Other Neurodegenerative Diseases. J Alzheimers Dis 27:615–625

    CAS  PubMed  Google Scholar 

  • Zohar AH, Dina C, Rosolio N, Osher Y, Gritsenko I, Bachner-Melman R, Benjamin J, Belmaker RH, Ebstein RP (2003) Tridimensional personality questionnaire trait of harm avoidance (anxiety proneness) is linked to a locus on chromosome 8p21. Am J Med Genet B Neuropsychiatr Genet 117B:66–69

    Article  PubMed  Google Scholar 

  • Zubenko GS, Maher BS, Hughes HB, Zubenko WN, Scott Stiffler J, Marazita ML (2004) Genome-wide linkage survey for genetic loci that affect the risk of suicide attempts in families with recurrent, early-onset, major depression. Am J Med Genet B Neuropsychiatr Genet 129B:47–54

    Article  PubMed  Google Scholar 

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Acknowledgments

Funding support for the (CIDR-COGA Study) was provided through the [the Center for Inherited Disease Research (CIDR) and the Collaborative Study on the Genetics of Alcoholism (COGA)]. The CIDR-COGA Study is a genome-wide association studies funded as part of the Collaborative Study on the Genetics of Alcoholism (COGA). Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the COGA. Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (COGA; U10 AA008401). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gap through dbGaP accession number: phs000125.v1.p1. Funding support for the SAGE was provided through the National Institutes of Health (NIH) Genes, Environment and Health Initiative (GEI) Grant U01 HG004422. SAGE is one of the GWAS funded as part of the GENEVA under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (Grant U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by COGA (Grant U10 AA008401), COGEND (Grant P01 CA089392), and FSCD (Grant R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by NIH GEI Grant U01HG004438, the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). The datasets used for the analyses described in this manuscript were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgibin/study.cgistudy_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p.1. This study was approved by Internal Review Board (IRB), East Tennessee State University.

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  1. Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, PO Box 70259, Lamb Hall, Johnson City, TN, 37614-1700, USA

    Amanda Taylor & Ke-Sheng Wang

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Correspondence to Ke-Sheng Wang.

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Taylor, A., Wang, KS. Association between DPYSL2 gene polymorphisms and alcohol dependence in Caucasian samples. J Neural Transm 121, 105–111 (2014). https://doi.org/10.1007/s00702-013-1065-2

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