Identification of susceptibility genes of Anorexia Nervosa by GWAS

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390191
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: International University of Health and Welfare
• Principal Investigator: KOMAKI Gen 国際医療福祉大学, 保健医療学部, 教授 (70225564)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 心療内科学 / 摂食障害

Research Abstract

Despite the high heritability of anorexia nervosa (AN), no causative gene has yet been pinpointed in the human genome. We tried to identify the causative genes in AN families using whole exon sequencing (exome analysis). This analysis found rare variants yielded substitution of amino acid and shared with affected individuals. Moreover, AN causative variants were likely to be accumulated at receptor genes for neurotransmitter. Of these, a rare varaint is expected to influence protein-protein interaction. Additional variants and functional analysis in the family genes will be prerequisite for future works.

Research Products

• [Journal Article] Divergence of East Asians and Europeans estimated using maleand female-specific genetic markers (2014)
  • Author(s): Tateno Y, Komiyama T, Katoh T, Munkhbat B, Oka A, Haida Y, Kobayashi H, Tamiya G, Inoko H
  • Journal Title: Genome Biol Evol Volume: 6(3) Pages: 466-73
  • DOI: 10.1093/gbe/evu027
  • Peer Reviewed
• [Journal Article] HLA-DRB1, -DRB3, -DRB4 and -DRB5 genotyping at a super-high resolution level by long range PCR and high-throughput sequencing (2014)
  • Author(s): Ozaki Y, Suzuki S, Shigenari A, Okudaira Y, Kikkawa E, Oka A, Ota M, Mitsunaga S, Kulski JK, Inoko H, Shiina T
  • Journal Title: Tissue Antigens Volume: 83(1) Pages: 10-6
  • DOI: 10.1111/tan.12258
  • Peer Reviewed
• [Journal Article] The Japanese Genetic Research Group For Eating Disorders. Association of the c.385C>A (p.Pro129Thr) polymorphism of the fatty acid amide hydrolase gene with anorexia nervosa in the Japanese population (2014)
  • Author(s): Ando T, Tamura N, Mera T, Morita C, Takei M, Nakamoto C, Koide M, Hotta M, Naruo T, Kawai K, Nakahara T, Yamaguchi C, Nagata T, Ookuma K, Okamoto Y, Yamanaka T, Kiriike N, Ichimaru Y, Ishikawa T, Komaki G
  • Journal Title: Molecular Genetics & Genomic Medicine
  • DOI: 10.1002/mgg3.69
  • Peer Reviewed
• [Journal Article] 摂食障害研究の最近の動向 (2014)
  • Author(s): 安藤哲也
  • Journal Title: 心身医学 Volume: 54(2) Pages: 146-153
• [Journal Article] IL12B and IL23R gene SNPs in Japanese psoriasis (2013)
  • Author(s): Oka A, Mabuchi T, Ikeda S, Terui T, Haida Y, Ozawa A, Yatsu K, Kulski JK, Inoko H
  • Journal Title: Immunogenetics Volume: 65(11) Pages: 823-8
  • DOI: 10.1007/s00251-013-0721-x
  • Peer Reviewed
• [Journal Article] Association analysis of the HLA-C gene in Japanese alopecia areata (2013)
  • Author(s): Haida Y, Ikeda S, Takagi A, Komiyama E, Mabuchi T, Ozawa A, Kulski JK, Inoko H, Oka A
  • Journal Title: Immunogenetics Volume: 65(7) Pages: 553-7
  • DOI: 10.1007/s00251-013-0703-z
  • Peer Reviewed
• [Journal Article] Japan Marrow Donor Programme (JMDP). Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation (2013)
  • Author(s): Harkensee C, Oka A, Onizuka M, Middleton PG, Inoko H, Nakaoka H, Gennery AR, Ando K, Morishima Y
  • Journal Title: Immunogenetics Volume: 65(6) Pages: 417-27
  • DOI: 10.1007/s00251-013-0691-z
  • Peer Reviewed
• [Journal Article] Improved loop-mediated isothermal amplification for HLA-DRB1 genotyping using RecA and a restriction enzyme for enhanced amplification specificity (2013)
  • Author(s): Mitsunaga S, Shimizu S, Okudaira Y, Oka A, Tanaka M, Kimura M, Kulski JK, Inoue I, Inoko H
  • Journal Title: Immunogenetics Volume: 65(6) Pages: 405-15
  • DOI: 10.1007/s00251-013-0690-0
  • Peer Reviewed
• [Journal Article] Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese (2013)
  • Author(s): Matsuzaka Y, Ohkubo T, Kikuti YY, Mizutani A, Tsuda M, Aoyama Y, Kakuta K, Oka A, Inoko H, Sakabe K, Ishikawa S, Kulski JK, Kimura M
  • Journal Title: Environ Toxicol
  • DOI: 10.1002/tox.21839
  • Peer Reviewed
• [Journal Article] (2013)
  • Author(s): Shibata H, Yamamoto K, Sun Z, Oka A, Inoko H, Arinami T, Inada T, Ujike H, Itokawa M, Tochigi M, Watanabe Y, Someya T, Kunugi H, Suzuki T, Iwata N, Ozaki N, Fukumaki Y
  • Journal Title: Psychiatr Genet Volume: 23(3) Pages: 117-23
  • DOI: 10.1097/YPG.0b013e32835fe4f1
  • Peer Reviewed
• [Journal Article] 摂食障害と遺伝子 (2013)
  • Author(s): 安藤哲也
  • Journal Title: 臨床精神医学 Volume: 42(5) Pages: 609-620
• [Journal Article] Super high resolution for single molecule-sequence-based typing of classical HLA loci at the 8-digit level using next generation sequencers (2012)
  • Author(s): Shiina T, Suzuki S, Ozaki Y, Taira H, Kikkawa E, Shigenari A, Oka A, Umemura T, Joshita S, Takahashi O, Hayashi Y, Paumen M, Katsuyama Y, Mitsunaga S, Ota M, Kulski JK, Inoko H
  • Journal Title: Tissue Antigens Volume: 80(4) Pages: 305-16
  • DOI: 10.1111/j.1399-0039.2012.01941.x
  • Peer Reviewed
• [Journal Article] Common variants in the COL4A4 gene confer susceptibility to lattice degeneration of the retina (2012)
  • Author(s): Meguro A, Ideta H, Ota M, Ito N, Ideta R, Yonemoto J, Takeuchi M, Uemoto R, Nishide T, Iijima Y, Kawagoe T, Okada E, Shiota T, Hagihara Y, Oka A, Inoko H, Mizuki N
  • Journal Title: PLoS One Volume: 7(6) Pages: e39300
  • DOI: 10.1371/journal.pone.0039300
  • Peer Reviewed
• [Journal Article] Japan Marrow Donor Program. Single nucleotide polymorphisms and outcome risk in unrelated mismatched hematopoietic stem cell transplantation : an exploration study (2012)
  • Author(s): Harkensee C, Oka A, Onizuka M, Middleton PG, Inoko H, Hirayasu K, Kashiwase K, Yabe T, Nakaoka H, Gennery AR, Ando K, Morishima Y
  • Journal Title: Blood Volume: 119(26) Pages: 6365-72
  • DOI: 10.1182/blood-2012-01-406785
  • Peer Reviewed
• [Journal Article] A systems genetics approach provides a bridge from discovered genetic variants to biological pathways in rheumatoid arthritis (2011)
  • Author(s): Nakaoka H, Cui T, Tajima A, Oka A, Mitsunaga S, Kashiwase K, Homma Y, Sato S, Suzuki Y, Inoko H, Inoue I
  • Journal Title: PLoS One Volume: 6(9) Pages: e25389
  • DOI: 10.1371/journal.pone.0025389
  • Peer Reviewed
• [Journal Article] A novel splicing variant of CADM2 as a protective transcript of psoriasis (2011)
  • Author(s): Hiruma A, Ikeda S, Terui T, Ozawa M, Hashimoto T, Yasumoto S, Nakayama J, Kubota Y, Iijima M, Sueki H, Matsumoto Y, Kato M, Akasaka E, Ikoma N, Mabuchi T, Tamiya S, Matsuyama T, Ozawa A, Inoko H, Oka A
  • Journal Title: Biochem Biophys Res Commun Volume: 412(4) Pages: 626-32
  • DOI: 10.1016/j.bbrc.2011.08.013
  • Peer Reviewed
• [Journal Article] Exact break point of a 50 kb deletion 8 kb centromeric of the HLA-A locus with HLA-A*24 : 02: the same deletion observed in other A*24 alleles and A*23:01 allele (2011)
  • Author(s): Mitsunaga S, Okudaira Y, Kunii N, Cui T, Hosomichi K, Oka A, Suzuki Y, Homma Y, Sato S, Inoue I, Inoko H
  • Journal Title: Immunogenetics Volume: 63(8) Pages: 467-74
  • DOI: 10.1007/s00251-011-0521-0
  • Peer Reviewed
• [Journal Article] Meta-analysis confirms the LCE3C_LCE3B deletion as a risk factor for psoriasis in several ethnic groups and finds interaction with HLA-Cw6 (2011)
  • Author(s): Riveira-Munoz E, He SM, Escaramís G, Stuart PE, Hüffmeier U, Lee C, Kirby B, Oka A, Giardina E, Liao W, Bergboer J, Kainu K, de Cid R, Munkhbat B, Zeeuwen PL, Armour JA, Poon A, Mabuchi T, Ozawa A, Zawirska A, Burden AD, Barker JN, Capon F, Traupe H, Sun LD, Cui Y, Yin XY, Chen G, Lim HW, Nair RP, Voorhees JJ, Tejasvi T, Pujol R, Munkhtuvshin N, Fischer J, Kere J, Schalkwijk J, Bowcock A, Kwok PY, Novelli G, Inoko H, Ryan AW, Trembath RC, Reis A, Zhang XJ, Elder JT, Estivill X
  • Journal Title: Invest Dermatol Volume: 131(5) Pages: 1105-9
  • DOI: 10.1038/jid.2010.350
  • Peer Reviewed
• [Journal Article] A genome-wide association study of anorexia nervosa
  • Author(s): Boraska V, Franklin CS, Floyd JA, Thornton LM, Huckins LM, Southam L, Rayner NW, Tachmazidou I, Klump KL, Treasure J, Lewis CM, Schmidt U, Tozzi F, Kiezebrink K, Hebebrand J, Gorwood P, Adan RA, Kas MJ, Favaro A, Santonastaso P, Fernández-Aranda F, Gratacos M, Rybakowski F, Dmitrzak-Weglarz M, Kaprio J, Keski-Rahkonen A, Raevuori A, Van Furth EF, Slof-Op 't Landt MC, Hudson JI, Reichborn-Kjennerud T, Knudsen GP, Monteleone P, Kaplan AS, Karwautz A, Hakonarson H, Berrettini WH, Guo Y, Li D, Schork NJ, Komaki G, Ando T, Inoko H, et al
  • Journal Title: Molecular Psychiatry
  • DOI: 10.1038/mp.2013.187
  • Peer Reviewed