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Genome-wide association study identifies aPSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C

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Abstract

Cytopenia during interferon-based (IFN-based) therapy for chronic hepatitis C (CHC) often necessitates reduction of doses of drugs and premature withdrawal from therapy resulting in poor response to treatment. To identify genetic variants associated with IFN-induced neutropenia, we conducted a genome-wide association study (GWAS) in 416 Japanese CHC patients receiving IFN-based therapy. Based on the results, we selected 192 candidate single nucleotide polymorphisms (SNPs) to carry out a replication analysis in an independent set of 404 subjects. The SNP rs2305482, located in the intron region of thePSMD3 gene on chromosome 17, showed a strong association when the results of GWAS and the replication stage were combined (OR = 2.18,P = 3.05 × 10−7 in the allele frequency model). Logistic regression analysis showed that rs2305482 CC and neutrophil count at baseline were independent predictive factors for IFN-induced neutropenia (OR = 2.497,P = 0.0072 and OR = 0.998,P < 0.0001, respectively). Furthermore, rs2305482 genotype was associated with the doses of pegylated interferon (PEG-IFN) that could be tolerated in hepatitis C virus genotype 1-infected patients treated with PEG-IFN plus ribavirin, but not with treatment efficacy. Our results suggest that genetic testing for this variant might be useful for establishing personalized drug dosing in order to minimize drug-induced adverse events.

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References

  • Bailly E, Reed SI (1999) Functional characterization of rpn3 uncovers a distinct 19S proteasomal subunit requirement for ubiquitin-dependent proteolysis of cell cycle regulatory proteins in budding yeast. Mol Cell Biol 19:6872–6890

    CAS PubMed Central PubMed  Google Scholar 

  • Crosslin DR, McDavid A, Weston N, Nelson SC, Zheng X, Hart E, de Andrade M, Kullo IJ, McCarty CA, Doheny KF, Pugh E, Kho A, Hayes MG, Pretel S, Saip A, Ritchie MD, Crawford DC, Crane PK, Newton K, Li R, Mirel DB, Crenshaw A, Larson EB, Carlson CS, Jarvik GP (2012) Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network. Hum Genet 131:639–652. doi:10.1007/s00439-011-1103-9

    Article PubMed Central PubMed  Google Scholar 

  • Fellay J, Thompson AJ, Ge D, Gumbs CE, Urban TJ, Shianna KV, Little LD, Qiu P, Bertelsen AH, Watson M, Warner A, Muir AJ, Brass C, Albrecht J, Sulkowski M, McHutchison JG, Goldstein DB (2010) ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 464:405–408. doi:10.1038/nature08825

    Article CAS PubMed  Google Scholar 

  • Ge D, Fellay J, Thompson AJ, Simon JS, Shianna KV, Urban TJ, Heinzen EL, Qiu P, Bertelsen AH, Muir AJ, Sulkowski M, McHutchison JG, Goldstein DB (2009) Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461:399–401. doi:10.1038/nature08309

    Article CAS PubMed  Google Scholar 

  • George SL, Bacon BR, Brunt EM, Mihindukulasuriya KL, Hoffmann J, Di Bisceglie AM (2009) Clinical, virologic, histologic, and biochemical outcomes after successful HCV therapy: a 5-year follow-up of 150 patients. Hepatology 49:729–738. doi:10.1002/hep.22694

    Article CAS PubMed Central PubMed  Google Scholar 

  • Jacobson IM, McHutchison JG, Dusheiko G, Di Bisceglie AM, Reddy KR, Bzowej NH, Marcellin P, Muir AJ, Ferenci P, Flisiak R, George J, Rizzetto M, Shouval D, Sola R, Terg RA, Yoshida EM, Adda N, Bengtsson L, Sankoh AJ, Kieffer TL, George S, Kauffman RS, Zeuzem S (2011) Telaprevir for previously untreated chronic hepatitis C virus infection. N Engl J Med 364:2405–2416. doi:10.1056/NEJMoa1012912

    Article CAS PubMed  Google Scholar 

  • Kamatani Y, Matsuda K, Okada Y, Kubo M, Hosono N, Daigo Y, Nakamura Y, Kamatani N (2010) Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet 42:210–215. doi:10.1038/ng.531

    Article CAS PubMed  Google Scholar 

  • Kurosaki M, Tanaka Y, Tanaka K, Suzuki Y, Hoshioka Y, Tamaki N, Kato T, Yasui Y, Hosokawa T, Ueda K, Tsuchiya K, Kuzuya T, Nakanishi H, Itakura J, Takahashi Y, Asahina Y, Matsuura K, Sugauchi F, Enomoto N, Nishida N, Tokunaga K, Mizokami M, Izumi N (2011) Relationship between polymorphisms of the inosine triphosphatase gene and anaemia or outcome after treatment with pegylated interferon and ribavirin. Antivir Ther 16:685–694. doi:10.3851/IMP1796

    Article CAS PubMed  Google Scholar 

  • Matsuura K, Tanaka Y, Watanabe T, Fujiwara K, Orito E, Kurosaki M, Izumi N, Sakamoto N, Enomoto N, Yatsuhashi H, Kusakabe A, Shinkai N, Nojiri S, Joh T, Mizokami M (2014) ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type. J Viral Hepat 21:466–474. doi:10.1111/jvh.12171

    Article CAS PubMed  Google Scholar 

  • McHutchison JG, Manns M, Patel K, Poynard T, Lindsay KL, Trepo C, Dienstag J, Lee WM, Mak C, Garaud JJ, Albrecht JK (2002) Adherence to combination therapy enhances sustained response in genotype-1-infected patients with chronic hepatitis C. Gastroenterology 123:1061–1069

    Article CAS PubMed  Google Scholar 

  • Nagata S, Tsuchiya M, Asano S, Kaziro Y, Yamazaki T, Yamamoto O, Hirata Y, Kubota N, Oheda M, Nomura H et al (1986) Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature 319:415–418. doi:10.1038/319415a0

    Article CAS PubMed  Google Scholar 

  • Nishida N, Tanabe T, Takasu M, Suyama A, Tokunaga K (2007) Further development of multiplex single nucleotide polymorphism typing method, the DigiTag2 assay. Anal Biochem 364:78–85. doi:10.1016/j.ab.2007.02.005

    Article CAS PubMed  Google Scholar 

  • Ochi H, Maekawa T, Abe H, Hayashida Y, Nakano R, Kubo M, Tsunoda T, Hayes CN, Kumada H, Nakamura Y, Chayama K (2010) ITPA polymorphism affects ribavirin-induced anemia and outcomes of therapy—a genome-wide study of Japanese HCV virus patients. Gastroenterology 139:1190–1197. doi:10.1053/j.gastro.2010.06.071

    Article CAS PubMed  Google Scholar 

  • Okada Y, Kamatani Y, Takahashi A, Matsuda K, Hosono N, Ohmiya H, Daigo Y, Yamamoto K, Kubo M, Nakamura Y, Kamatani N (2010) Common variations in PSMD3-CSF3 and PLCB4 are associated with neutrophil count. Hum Mol Genet 19:2079–2085. doi:10.1093/hmg/ddq080

    Article CAS PubMed  Google Scholar 

  • Poordad F, Bronowicki JP, Gordon SC, Zeuzem S, Jacobson IM, Sulkowski MS, Poynard T, Morgan TR, Molony C, Pedicone LD, Sings HL, Burroughs MH, Sniukiene V, Boparai N, Goteti VS, Brass CA, Albrecht JK, Bacon BR (2012) Factors that predict response of patients with hepatitis C virus infection to boceprevir. Gastroenterology 143(608–18):e1–e5. doi:10.1053/j.gastro.2012.05.011

    PubMed  Google Scholar 

  • Reiner AP, Lettre G, Nalls MA, Ganesh SK, Mathias R, Austin MA, Dean E, Arepalli S, Britton A, Chen Z, Couper D, Curb JD, Eaton CB, Fornage M, Grant SF, Harris TB, Hernandez D, Kamatini N, Keating BJ, Kubo M, LaCroix A, Lange LA, Liu S, Lohman K, Meng Y, Mohler ER 3rd, Musani S, Nakamura Y, O’Donnell CJ, Okada Y, Palmer CD, Papanicolaou GJ, Patel KV, Singleton AB, Takahashi A, Tang H, Taylor HA Jr, Taylor K, Thomson C, Yanek LR, Yang L, Ziv E, Zonderman AB, Folsom AR, Evans MK, Liu Y, Becker DM, Snively BM, Wilson JG (2011) Genome-wide association study of white blood cell count in 16,388 African Americans: the continental origins and genetic epidemiology network (COGENT). PLoS Genet 7:e1002108. doi:10.1371/journal.pgen.1002108

    Article CAS PubMed Central PubMed  Google Scholar 

  • Sakamoto N, Tanaka Y, Nakagawa M, Yatsuhashi H, Nishiguchi S, Enomoto N, Azuma S, Nishimura-Sakurai Y, Kakinuma S, Nishida N, Tokunaga K, Honda M, Ito K, Mizokami M, Watanabe M (2010) ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C. Hepatol Res 40:1063–1071. doi:10.1111/j.1872-034X.2010.00741.x

    Article CAS PubMed  Google Scholar 

  • Soranzo N, Spector TD, Mangino M, Kuhnel B, Rendon A, Teumer A, Willenborg C, Wright B, Chen L, Li M, Salo P, Voight BF, Burns P, Laskowski RA, Xue Y, Menzel S, Altshuler D, Bradley JR, Bumpstead S, Burnett MS, Devaney J, Doring A, Elosua R, Epstein SE, Erber W, Falchi M, Garner SF, Ghori MJ, Goodall AH, Gwilliam R, Hakonarson HH, Hall AS, Hammond N, Hengstenberg C, Illig T, Konig IR, Knouff CW, McPherson R, Melander O, Mooser V, Nauck M, Nieminen MS, O’Donnell CJ, Peltonen L, Potter SC, Prokisch H, Rader DJ, Rice CM, Roberts R, Salomaa V, Sambrook J, Schreiber S, Schunkert H, Schwartz SM, Serbanovic-Canic J, Sinisalo J, Siscovick DS, Stark K, Surakka I, Stephens J, Thompson JR, Volker U, Volzke H, Watkins NA, Wells GA, Wichmann HE, Van Heel DA, Tyler-Smith C, Thein SL, Kathiresan S, Perola M, Reilly MP, Stewart AF, Erdmann J, Samani NJ, Meisinger C, Greinacher A, Deloukas P, Ouwehand WH, Gieger C (2009) A genome-wide meta-analysis identifies 22 loci associated with eight hematological parameters in the HaemGen consortium. Nat Genet 41:1182–1190. doi:10.1038/ng.467

    Article CAS PubMed Central PubMed  Google Scholar 

  • Suppiah V, Moldovan M, Ahlenstiel G, Berg T, Weltman M, Abate ML, Bassendine M, Spengler U, Dore GJ, Powell E, Riordan S, Sheridan D, Smedile A, Fragomeli V, Muller T, Bahlo M, Stewart GJ, Booth DR, George J (2009) IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet 41:1100–1104. doi:10.1038/ng.447

    Article CAS PubMed  Google Scholar 

  • Tanaka Y, Nishida N, Sugiyama M, Kurosaki M, Matsuura K, Sakamoto N, Nakagawa M, Korenaga M, Hino K, Hige S, Ito Y, Mita E, Tanaka E, Mochida S, Murawaki Y, Honda M, Sakai A, Hiasa Y, Nishiguchi S, Koike A, Sakaida I, Imamura M, Ito K, Yano K, Masaki N, Sugauchi F, Izumi N, Tokunaga K, Mizokami M (2009) Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet 41:1105–1109. doi:10.1038/ng.449

    Article CAS PubMed  Google Scholar 

  • Tanaka Y, Kurosaki M, Nishida N, Sugiyama M, Matsuura K, Sakamoto N, Enomoto N, Yatsuhashi H, Nishiguchi S, Hino K, Hige S, Itoh Y, Tanaka E, Mochida S, Honda M, Hiasa Y, Koike A, Sugauchi F, Kaneko S, Izumi N, Tokunaga K, Mizokami M (2011) Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C. Hum Mol Genet 20:3507–3516. doi:10.1093/hmg/ddr249

    Article CAS PubMed  Google Scholar 

  • Thompson AJ, Clark PJ, Singh A, Ge D, Fellay J, Zhu M, Zhu Q, Urban TJ, Patel K, Tillmann HL, Naggie S, Afdhal NH, Jacobson IM, Esteban R, Poordad F, Lawitz EJ, McCone J, Shiffman ML, Galler GW, King JW, Kwo PY, Shianna KV, Noviello S, Pedicone LD, Brass CA, Albrecht JK, Sulkowski MS, Goldstein DB, McHutchison JG, Muir AJ (2012) Genome-wide association study of interferon-related cytopenia in chronic hepatitis C patients. J Hepatol 56:313–319. doi:10.1016/j.jhep.2011.04.021

    Article CAS PubMed Central PubMed  Google Scholar 

  • Yang TP, Beazley C, Montgomery SB, Dimas AS, Gutierrez-Arcelus M, Stranger BE, Deloukas P, Dermitzakis ET (2010) Genevar: a database and Java application for the analysis and visualization of SNP-gene associations in eQTL studies. Bioinformatics 26:2474–2476. doi:10.1093/bioinformatics/btq452

    Article CAS PubMed Central PubMed  Google Scholar 

  • Yoshida H, Tateishi R, Arakawa Y, Sata M, Fujiyama S, Nishiguchi S, Ishibashi H, Yamada G, Yokosuka O, Shiratori Y, Omata M (2004) Benefit of interferon therapy in hepatocellular carcinoma prevention for individual patients with chronic hepatitis C. Gut 53:425–430

    Article CAS PubMed Central PubMed  Google Scholar 

  • Zeuzem S, Andreone P, Pol S, Lawitz E, Diago M, Roberts S, Focaccia R, Younossi Z, Foster GR, Horban A, Ferenci P, Nevens F, Mullhaupt B, Pockros P, Terg R, Shouval D, van Hoek B, Weiland O, Van Heeswijk R, De Meyer S, Luo D, Boogaerts G, Polo R, Picchio G, Beumont M (2011) Telaprevir for retreatment of HCV infection. N Engl J Med 364:2417–2428. doi:10.1056/NEJMoa1013086

    Article CAS PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Yasuka Uehara-Shibata, Yuko Ogasawara-Hirano, Yoshimi Ishibashi, Natsumi Baba, Megumi Yamaoka-Sageshima, Takayo Tsuchiura, Yoriko Mawatari (Tokyo University), and Dr. Shintaro Ogawa (Nagoya City University) for technical assistance. This work was supported by the Ministry of Health, Labor, and Welfare of Japan (H25-kanen-ippan-005) to Yasuhito Tanka and Katsushi Tokunaga, KAKENHI (22133008) Grant-in-Aid for Scientific Research on Innovative Areas to Katsushi Tokunaga, and KAKENHI (24790728) Grant-in-Aid from the Ministry of Education, Culture, Sports, Science of Japan for Young Scientists (B) to Nao Nishida.

Conflict of interest

The following authors are currently conducting research sponsored by the companies: Yasuhito Tanaka, Keisuke Hino, and Yoshito Itoh by Merck Sharp & Dohme, Corp., Chugai Pharmaceutical Co., Ltd., and Bristol-Myers Squibb; Nobuyuki Enomoto, Shuhei Nishiguchi, and Eiji Tanaka by Merck Sharp & Dohme, Corp. and Chugai Pharmaceutical Co., Ltd.; Naoya Sakamoto by Chugai Pharmaceutical Co., Ltd, Bristol-Myers Squibb, Merck Sharp & Dohme, Corp., and Otsuka Pharmaceutical Co., Ltd.; Hiroshi Yatsuhashi by Chugai Pharmaceutical Co., Ltd.; Akihiro Tamori by Merck Sharp & Dohme, Corp.; Satoshi Mochida by Merck Sharp & Dohme, Corp., Chugai Pharmaceutical Co., Ltd., Bristol-Myers Squibb, and Toray Medical Co., Ltd. The other authors have no conflict of interest.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Virology and Liver Unit, Nagoya City University Graduate School of Medical Sciences, Kawasumi, Mizuho, Nagoya, 467-8601, Japan

    Etsuko Iio, Kentaro Matsuura & Yasuhito Tanaka

  2. Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, 467-8601, Japan

    Etsuko Iio & Kentaro Matsuura

  3. The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, 272-8516, Japan

    Nao Nishida & Naohiko Masaki

  4. Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, 113-0033, Japan

    Nao Nishida & Katsushi Tokunaga

  5. First Department of Internal Medicine, University of Yamanashi, Chuo, 409-3898, Japan

    Shinya Maekawa & Nobuyuki Enomoto

  6. Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, 113-0034, Japan

    Mina Nakagawa & Naoya Sakamoto

  7. Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, 060-0814, Japan

    Naoya Sakamoto & Shuhei Hige

  8. Clinical Research Center, National Nagasaki Medical Center, Omura, 856-8562, Japan

    Hiroshi Yatsuhashi

  9. Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, 180-0023, Japan

    Masayuki Kurosaki & Namiki Izumi

  10. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan

    Yoichi Hiasa

  11. Division of Gastroenterology, Department of Medicine, Kurume University, Kurume, 830-0011, Japan

    Tatsuya Ide

  12. Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, 701-0114, Japan

    Keisuke Hino

  13. Department of Hepatology, Osaka City Graduate School of Medicine, Osaka, 545-8585, Japan

    Akihiro Tamori

  14. Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-0934, Japan

    Masao Honda & Shuichi Kaneko

  15. Division of Gastroenterology and Hepatology, Internal Medicine, Saitama Medical University, Iruma, 350-0495, Japan

    Satoshi Mochida

  16. The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, 803-8505, Japan

    Hideyuki Nomura

  17. Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, 663-8131, Japan

    Shuhei Nishiguchi

  18. Department of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, 216-8511, Japan

    Chiaki Okuse

  19. Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan

    Yoshito Itoh

  20. Third Department of Internal Medicine, Nara Medical University, Kashihara, 634-8522, Japan

    Hitoshi Yoshiji

  21. Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, 755-8505, Japan

    Isao Sakaida

  22. Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, 700-0914, Japan

    Kazuhide Yamamoto

  23. Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, 990-9585, Japan

    Hisayoshi Watanabe

  24. Department of Gastroenterology, Sapporo Kosei General Hospital, Sapporo, 060-0033, Japan

    Shuhei Hige

  25. Department of Medicine, Shinshu University School of Medicine, Matsumoto, 390-8621, Japan

    Akihiro Matsumoto & Eiji Tanaka

Authors
  1. Etsuko Iio

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  2. Kentaro Matsuura

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  3. Nao Nishida

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  4. Shinya Maekawa

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  5. Nobuyuki Enomoto

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  6. Mina Nakagawa

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  7. Naoya Sakamoto

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  8. Hiroshi Yatsuhashi

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  9. Masayuki Kurosaki

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  10. Namiki Izumi

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  11. Yoichi Hiasa

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  12. Naohiko Masaki

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  13. Tatsuya Ide

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  14. Keisuke Hino

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  15. Akihiro Tamori

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  16. Masao Honda

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  17. Shuichi Kaneko

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  18. Satoshi Mochida

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  19. Hideyuki Nomura

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  20. Shuhei Nishiguchi

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  21. Chiaki Okuse

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  22. Yoshito Itoh

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  23. Hitoshi Yoshiji

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  24. Isao Sakaida

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  25. Kazuhide Yamamoto

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  26. Hisayoshi Watanabe

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  27. Shuhei Hige

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  28. Akihiro Matsumoto

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  29. Eiji Tanaka

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  30. Katsushi Tokunaga

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  31. Yasuhito Tanaka

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Corresponding author

Correspondence toYasuhito Tanaka.

Additional information

E. Iio and K. Matsuura equally contributed to this work (shared first authorship).

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Iio, E., Matsuura, K., Nishida, N.et al. Genome-wide association study identifies aPSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.Hum Genet134, 279–289 (2015). https://doi.org/10.1007/s00439-014-1520-7

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