Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies

Abstract

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data. In this article, the reliability of our data was evaluated by principal component analysis (PCA) and association analysis for hematological and biochemical traits by using genome-wide SNP data. PCA of the SNPs showed that all the samples were collected from the Japanese population and that the samples were separated into two major clusters by birthplace, Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs that have been reported to be associated with 18 hematological and biochemical traits in genome-wide association studies (GWAS), the associations of 56 SNPs were replicated using our data base. Statistical power simulations showed that the sample size of the JPDSC control database is large enough to detect genetic markers having a relatively strong association even when the case sample size is small. The JPDSC database will be useful as control data for conducting PGx studies to explore genetic markers to improve the safety and efficacy of drugs either during clinical development or in post-marketing.

Knowledge and attitudes on pharmacogenetics among pediatricians

“…The Japan Society of Human Genetics, Japanese Society of Clinical Pharmacology and Therapeutics, and Japanese Committee for Clinical Laboratory Standards subsequently published clinical pharmacogenetic guidelines in 2010 [23]. Moreover, the Japan Pharmacogenomics Data Science Consortium was established in 2009 by six pharmaceutical companies (Astellas, Daiichi Sankyo, Mitsubishi Tanabe, Otsuka, Taisho, and Takeda) with the aim of supporting pharmacogenomic discovery in Japan during drug development and post-market [24]. Consistent with these efforts, 81.0% of the general Japanese public previously reported a positive attitude towards pharmacogenetics research [25].…”

HLA‐B*51:01 and CYP2C9*3 Are Risk Factors for Phenytoin‐Induced Eruption in the Japanese Population: Analysis of Data From the Biobank Japan Project

“…Therefore, CYP2C9*3 carrier status would be sufficient to decrease the probability of adverse reactions associated with phenytoin in the Japanese population. The HLA‐B*15:02 frequency in the Japanese population was reported to be 0.0002–0.001; thus, the clinical utility of the allele in Japanese is quite low . Conversely, the HLA‐B*51:01 allele frequencies in Japanese was reported to be 0.077–0.083 .…”

“…The Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Royal Dutch Association for the Advancement of Pharmacy‐Pharmacogenetics Working Group (DPWG) are well known for clinical support provision . However, these guidelines have not been utilized in clinical practice in Japan, given the lack of evidence of the associations with CYP2C9 and extremely low HLA‐B*15:02 frequency in its population . Recently, Su et al reported the associations of phenytoin‐induced hypersensitivity with CYP2C9*3 and HLA‐B alleles in some East Asian populations; however, no HLA‐B alleles showed significant associations in the Japanese population, specifically.…”

Independent association of HLA-DPB1*02:01 with rheumatoid arthritis in Japanese populations

“…RA patients fulfilled the 1987 American College of Rheumatology criteria for RA [ 24 ] or the 2010 Rheumatoid Arthritis Classification Criteria [ 25 ]. Four hundred thirteen Japanese healthy controls (mean age ± SD, 39.3 ± 11.0 years, vs. ACPA(+)RA: P = 6.50X10 -130 , vs. ACPA(-)RA, P = 5.51X10 -71 , 61 male [14.8%], vs. ACPA(+)RA: P = 0.0792, vs. ACPA(-)RA, P = 0.2195) were recruited at Kanazawa University, Sagamihara National Hospital, and Teikyo University [ 26 ] or by the Pharma SNP Consortium (Tokyo, Japan) [ 27 , 28 ]. Rheumatoid factor and ACPA were measured by N-latex RF kit (Siemens Healthcare Diagnostics, München, Germany) or Mesacup-2 test CCP (Medical & Biological Laboratories, Nagoya, Japan), respectively.…”