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ID 115836
Nakayama, Akiyoshi National Defense Medical College|Japan Air Self-Defense Force
Nakatochi, Masahiro Nagoya University
Kawamura, Yusuke National Defense Medical College
Yamamoto, Ken Kurume University
Nakaoka, Hirofumi National Institute of Genetics
Shimizu, Seiko National Defense Medical College
Higashino, Toshihide National Defense Medical College|Hokkaido University
Koyama, Teruhide Kyoto Prefectural University of Medicine
Hishida, Asahi Nagoya University
Kuriki, Kiyonori University of Shizuoka
Watanabe, Miki Nagoya City University
Shimizu, Toru Midorigaoka Hospital|Kyoto Industrial Health Association
Ooyama, Keiko Ryougoku East Gate Clinic
Ooyama, Hiroshi Ryougoku East Gate Clinic
Nagase, Mitsuo Nagase Clinic
Hidaka, Yuji Akasaka Central Clinic
Matsui, Daisuke Kyoto Prefectural University of Medicine
Tamura, Takashi Nagoya University
Nishiyama, Takeshi Nagoya City University
Shimanoe, Chisato Saga University
Takashima, Naoyuki Shiga University of Medical Science|Kindai University
Shirai, Yuya Osaka University
Kawaguchi, Makoto National Defense Medical College
Takao, Mikiya National Defense Medical College
Sugiyama, Ryo National Defense Medical College
Takada, Yuzo Teikyo University of Science
Nakamura, Takahiro National Defense Medical College
Nakashima, Hiroshi National Defense Medical College
Tsunoda, Masashi National Defense Medical College
Danjoh, Inaho Tohoku Medical Megabank Organization
Hozawa, Atsushi Tohoku Medical Megabank Organization
Hosomichi, Kazuyoshi Kanazawa University
Toyoda, Yu The University of Tokyo
Kubota, Yu The University of Tokyo
Takada, Tappei The University of Tokyo
Suzuki, Hiroshi The University of Tokyo
Stiburkova, Blanka Charles University|General University Hospital|Institute of Rheumatology, Prague
Major, Tanya J. University of Otago
Merriman, Tony R. University of Otago
Kuriyama, Nagato Kyoto Prefectural University of Medicine
Mikami, Haruo Chiba Cancer Center Research Institute
Takezaki, Toshiro Kagoshima University
Matsuo, Keitaro Aichi Cancer Center Research Institute|Nagoya University
Suzuki, Sadao Nagoya City University
Hosoya, Tatsuo Jikei University School of Medicine
Kamatani, Yoichiro RIKEN|Kyoto University
Kubo, Michiaki RIKEN
Ichida, Kimiyoshi Jikei University School of Medicine|Tokyo University of Pharmacy and Life Science
Wakai, Kenji Nagoya University
Inoue, Ituro National Institute of Genetics
Okada, Yukinori Osaka University
Shinomiya, Nariyoshi National Defense Medical College
Matsuo, Hirotaka National Defense Medical College
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Journal Article
Genome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years.
Two genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype.
In addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p<5.0×10–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout.
Our findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.
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Annals of the Rheumatic Diseases
BMJ Publishing Group
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This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:
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Medical Sciences