title: [Pharmacogenomics study of 620 whole-exome sequencing: focusing on aspirin application].
abstract: OBJECTIVE
  To investigate the allele frequencies of aspirin-response-related variants in different population.
  
  
  METHODS
  The allele frequencies of reported clinically significant aspirin-response-related variants were evaluated based on 620 whole exome sequencing (WES) data collected from 2013 to 2016 in Children's Hospital of Fudan University.Then the local allele frequencies were compared with 1 000 Genomes project database, and χ(2) test was used.
  
  
  RESULTS
  Thirty-eight aspirin-response-related variants that had clinical significance had been detected in the 620 WES data.Ten (26%) of them were related with drug efficacy while 28 (74%) were related with toxicity or adverse drug reaction (ADR). These variants were distributed in 33 genes.There were 23 aspirin-related variants further analysised, and the frequency of 7 (rs1050891, rs6065, rs7862221, rs1065776, rs3818822, rs3775291 and rs1126643) had no significant difference compared with frequency of European and East Asian population of 1 000 Genome project (P>0.01 for both), 10 (rs2228079, rs1613662, rs4523, rs28360521, rs1131882, rs1047626, rs3856806, rs2768759, rs7572857 and rs1126510) of them had no significant difference compared with East Asian but were significantly different from European population, 1 (rs2075797) had no significant difference compared with frequency of European and different with frequency of East Asian, and 5 variants(rs10279545, rs730012, rs16851030, rs1353411, rs1800469)were different from frequency of both East Asian(0.019, 0.058, 0.167, 0.452, 0.340 vs. 0.100, 0.151, 0.396, 0.568, 0.453, χ(2)=21.798, 20.400, 67.543, 16.531, 15.807, P all<0.01) and European population(0.531, 0.312, 0.037, 0.179, 0.688, χ(2)=325.799, 92.877, 144.811, 156.471, 174.533, P all<0.01).
  
  
  CONCLUSIONS
  Most variants that have clinical significance in aspirin response are related with drug efficacy or drug toxicity or ADR, indicating the urgency of variants screen in clinical practice.Significant population-specificity is detected in local 620 WES data in aspirin-response-related variants.
authors.affiliation: Department of Endocrinology and Genetics, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Birth Defects, Children's Hospital of Fudan University, Shanghai 201102, China.
authors.forename: Y L
authors.initials: YL
authors.lastname: Lu
authors.forename: H J
authors.initials: HJ
authors.lastname: Wang
authors.forename: W H
authors.initials: WH
authors.lastname: Zhou
mesh_terms: D044466:Asian People; D001241:Aspirin / Q000009:adverse effects*; D002648:Child; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D059472:Exome; D005787:Gene Frequency; D006801:Humans; D010597:Pharmacogenetics
chemical_list: D001241:Aspirin