Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients
| العنوان: | Subtype-specific gout susceptibility loci and enrichment of selection pressure on ABCG2 and ALDH2 identified by subtype genome-wide meta-analyses of clinically defined gout patients |
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| المؤلفون: | Akiyoshi, Nakayama, Masahiro, Nakatochi, Yusuke, Kawamura, Ken, Yamamoto, Hirofumi, Nakaoka, Seiko, Shimizu, Toshihide, Higashino, Teruhide, Koyama, Asahi, Hishida, Kiyonori, Kuriki, Miki, Watanabe, Toru, Shimizu, Keiko, Ooyama, Hiroshi, Ooyama, Mitsuo, Nagase, Yuji, Hidaka, Daisuke, Matsui, Takashi, Tamura, Takeshi, Nishiyama, Chisato, Shimanoe, Sakurako, Katsuura-Kamano, Naoyuki, Takashima, Yuya, Shirai, Makoto, Kawaguchi, Mikiya, Takao, Ryo, Sugiyama, Yuzo, Takada, Takahiro, Nakamura, Hiroshi, Nakashima, Masashi, Tsunoda, Inaho, Danjoh, Atsushi, Hozawa, Kazuyoshi, Hosomichi, Yu, Toyoda, Yu, Kubota, Tappei, Takada, Hiroshi, Suzuki, Blanka, Stiburkova, Tanya J, Major, Tony R, Merriman, Nagato, Kuriyama, Haruo, Mikami, Toshiro, Takezaki, Keitaro, Matsuo, Sadao, Suzuki, Tatsuo, Hosoya, Yoichiro, Kamatani, Michiaki, Kubo, Kimiyoshi, Ichida, Kenji, Wakai, Ituro, Inoue, Yukinori, Okada, Nariyoshi, Shinomiya, Hirotaka, Matsuo, Tatsuya, Saitoh |
| المصدر: | Annals of the Rheumatic Diseases |
| بيانات النشر: | BMJ Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Crystal Arthropathies, Gout, Genome-wide association study, Bioinformatics, Severity of Illness Index, Genome, 0302 clinical medicine, Japan, Reference Values, Genotype, ATP Binding Cassette Transporter, Subfamily G, Member 2, Immunology and Allergy, Medicine, Aldehyde Dehydrogenase, Mitochondrial, Incidence, selection pressure analysis, Prognosis, Phenotype, Neoplasm Proteins, musculoskeletal diseases, Immunology, Risk Assessment, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Asian People, Humans, Genetic Predisposition to Disease, Genetic association, ALDH2, subtype specific locus, business.industry, nutritional and metabolic diseases, genome-wide association study (GWAS), medicine.disease, gout/hyperuricaemia, 030104 developmental biology, Genetic Loci, Case-Control Studies, Japanese, business, 030217 neurology & neurosurgery, Imputation (genetics), Genome-Wide Association Study |
| الوصف: | ObjectivesGenome-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.MethodsTwo 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.ResultsIn addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p–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.ConclusionsOur 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1468-2060 0003-4967 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::959d9198efe32f30ca31f7658993adf0 http://europepmc.org/articles/PMC7213308 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....959d9198efe32f30ca31f7658993adf0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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