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Association between AUTS2 haplotypes and alcohol dependence in a Japanese population

  • Shin Narita (a1), Kenta Nagahori (a2), Daisuke Nishizawa (a3), Eiji Yoshihara (a1), Atsuko Kawai (a4), Kazutaka Ikeda (a3) and Kazuhiko Iwahashi (a1) (a3) (a5)...



Recent genome-wide analysis has indicated that the autism susceptibility candidate 2 (AUTS2) gene is involved in the regulation of alcohol consumption. We hypothesised that AUTS2 might be associated with the development of alcohol dependence. Therefore, in this exploratory study, we compared the genotype and allele frequencies of the polymorphisms rs6943555 and rs9886351 in the AUTS2 gene between patients with alcohol dependence and healthy control subjects living in a Japanese provincial prefecture. We also examined whether or not the haplotypes consisting of these polymorphisms are related to alcohol dependence.


The subjects of this study consisted of 64 patients with alcohol dependence and 75 unrelated healthy people. The AUTS2 genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method.


No significant differences in the genotype and allele frequencies of the polymorphisms AUTS2 rs6943555 and rs9886351 were found between alcohol dependence and control subjects. On the other hand, the frequencies of the AUTS2 haplotypes were significantly different between them, and the rs6943555 and rs9886351 A-A haplotype was associated with alcohol dependence (p=0.0187).


This suggests that the rs6943555 and rs9886351 A-A haplotype might affect the vulnerability to alcohol dependence pathogenesis. Further studies are needed to confirm the reproducibility of the results of this study with increased numbers of subjects.


Corresponding author

Kazuhiko Iwahashi, Laboratory of Physiology (Project of Neurophysiology), the Graduate School of Environmental Health Sciences, Azabu University, 1-17-71 Fuchinobe, Chuo-ku, Sagamihara-shi, Kanagawa 252-5201, Japan. Tel: +81 42 769 1930; Fax: +81 42 769 1930; E-mail:


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1. Nishizawa, D, Han, W, Hasegawa, J et al. Association of mu-opioid receptor gene polymorphism A118G with alcohol dependence in a Japanese population. Neuropsychobiology 2006;53:137141.
2. Agrawal, A, Lynskey, MT. Are there genetic influences on addiction: evidence from family, adoption and twin studies. Addiction 2008;103:10691081.
3. Enoch, MA, Goldman, D. The genetics of alcoholism and alcohol abuse. Curr Psychiatry Rep 2001;3:144151.
4. Goldman, D, Oroszi, G, Ducci, F. The genetics of addictions: uncovering the genes. Nat Rev Genet 2005;6:521532.
5. Oksenberg, N, Ahituv, N. The role of AUTS2 in neurodevelopment and human evolution. Trends Genet 2013;29:600608.
6. Ben-David, E, Granot-Hershkovitz, E, Monderer-Rothkoff, G et al. Identification of a functional rare variant in autism using genome-wide screen for monoallelic expression. Hum Mol Genet 2011;20:36323641.
7. Zhang, B, Xu, YH, Wei, SG et al. Association study identifying a new susceptibility gene (AUTS2) for schizophrenia. Int J Mol Sci 2014;15:1940619416.
8. Chojnicka, I, Gajos, K, Strawa, K et al. Possible association between suicide committed under influence of ethanol and a variant in the AUTS2 gene. PLoS One 2013;8:e57199.
9. Philibert, RA, Ryu, GY, Yoon, JG et al. Transcriptional profiling of subjects from the Iowa adoption studies. Am J Med Genet B Neuropsychiatr Genet 2007;144B:683690.
10. Chen, YH, Liao, DL, Lai, CH, Chen, CH. Genetic analysis of AUTS2 as a susceptibility gene of heroin dependence. Drug Alcohol Depend 2013;128:238242.
11. Dang, W, Zhang, Q, Zhu, YS, Lu, XY. The evidence for the contribution of the autism susceptibility candidate 2 (AUTS2) gene in heroin dependence susceptibility. J Mol Neurosci 2014;54:811819.
12. Schumann, G, Coin, LJ, Lourdusamy, A et al. Genome-wide association and genetic functional studies identify autism susceptibility candidate 2 gene (AUTS2) in the regulation of alcohol consumption. Proc Natl Acad Sci USA 2011;108:71197124.
13. de Bakker, PI, Yelensky, R, Pe’er, I, Gabriel, SB, Daly, MJ, Altshuler, D. Efficiency and power in genetic association studies. Nat Genet 2005;37:12171223.
14. Barrett, JC, Fry, B, Maller, J, Daly, MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263265.
15. Purcell, S, Neale, B, Todd-Brown, K et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007;81:559575.
16. Schuckit, MA, Smith, TL, Kalmijn, J. The search for genes contributing to the low level of response to alcohol: patterns of findings across studies. Alcohol Clin Exp Res 2004;28:14491458.
17. Morris, RW, Kaplan, NL. On the advantage of haplotype analysis in the presence of multiple disease susceptibility alleles. Genet Epidemiol 2002;23:221233.
18. You, J, Yuan, Y, Zhang, Z, Zhang, X, Li, H, Qian, Y. A preliminary association study between brain-derived neurotrophic factor (BDNF) haplotype and late-onset depression in mainland Chinese. J Affect Disord 2010;120:165169.
19. Nyholt, DR. Genetic case-control association studies – correcting for multiple testing. Hum Genet 2001;109:564567.
20. Perneger, TV. What’s wrong with Bonferroni adjustments. BMJ 1998;316:12361238.



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