title: Proficiency testing of human leukocyte antigen-DR and human leukocyte antigen-DQ genetic risk assessment for type 1 diabetes using dried blood spots.
abstract: BACKGROUND
  The plurality of genetic risk for developing type 1 diabetes mellitus (T1DM) lies within the genes that code for the human leukocyte antigens (HLAs). Many T1DM studies use HLA genetic risk assessment to identify higher risk individuals, and they often conduct these tests on dried blood spots (DBSs) like those used for newborn bloodspot screening. One such study is The Environmental Determinants of Diabetes in the Young (TEDDY), a long-term prospective study of environmental risk factors. To provide quality assurance for T1DM studies that employ HLA genetic risk assessment, the Centers for Disease Control and Prevention (CDC) conducts both a voluntary quarterly proficiency testing (VQPT) program available to any laboratory and a mandatory annual proficiency testing (PT) challenge for TEDDY laboratories.
  
  
  METHODS
  Whole blood and DBS samples with a wide range of validated HLA-DR and HLA-DQ genotypes were sent to the participating laboratories. Results were evaluated on the basis of both the reported haplotypes and the HLA genetic risk assessment.
  
  
  RESULTS
  Of the reported results from 24 panels sent out over six years in the VQPT, 94.7% (857/905) were correctly identified with respect to the relevant HLA-DR or HLA-DQ alleles, and 96.4% (241/250) were correctly categorized for risk assessment. Significant improvement was seen over the duration of this program, usually reaching 100% correct categorization during the last three years. Of 1154 reported results in four TEDDY PT challenges, 1153 (99.9%) were correctly identified for TEDDY eligibility.
  
  
  CONCLUSIONS
  The different analytical methods used by T1DM research centers all provided accurate (>99%) results for genetic risk assessment. The two CDC PT programs documented the validity of the various approaches to screening and contributed to overall quality assurance.
authors.affiliation: Division of Laboratory Sciences, Centers for Disease Control and Prevention, Atlanta, Georgia 30341, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Dantonio
authors.forename: Nancy
authors.initials: N
authors.lastname: Meredith-Molloy
authors.forename: William A
authors.initials: WA
authors.lastname: Hagopian
authors.forename: Jin Xiong
authors.initials: JX
authors.lastname: She
authors.forename: Beena
authors.initials: B
authors.lastname: Akolkar
authors.forename: Suzanne K
authors.initials: SK
authors.lastname: Cordovado
authors.forename: Miyono
authors.initials: M
authors.lastname: Hendrix
authors.forename: L Omar
authors.initials: LO
authors.lastname: Henderson
authors.forename: W Harry
authors.initials: WH
authors.lastname: Hannon
authors.forename: Robert F
authors.initials: RF
authors.lastname: Vogt
mesh_terms: D000328:Adult; D002900:Chromosomes, Human, 1-3 / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006683:HLA-DQ Antigens / Q000097:blood*; D006684:HLA-DR Antigens / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D007962:Leukocytes / Q000737:chemistry*; D011237:Predictive Value of Tests; D012015:Reference Standards; D018570:Risk Assessment
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens