title: Confirmation of novel type 1 diabetes risk loci in families.
abstract: OBJECTIVE
  Over 50 regions of the genome have been associated with type 1 diabetes risk, mainly using large case/control collections. In a recent genome-wide association (GWA) study, 18 novel susceptibility loci were identified and replicated, including replication evidence from 2,319 families. Here, we, the Type 1 Diabetes Genetics Consortium (T1DGC), aimed to exclude the possibility that any of the 18 loci were false-positives due to population stratification by significantly increasing the statistical power of our family study.
  
  
  METHODS
  We genotyped the most disease-predicting single-nucleotide polymorphisms at the 18 susceptibility loci in 3,108 families and used existing genotype data for 2,319 families from the original study, providing 7,013 parent-child trios for analysis. We tested for association using the transmission disequilibrium test.
  
  
  RESULTS
  Seventeen of the 18 susceptibility loci reached nominal levels of significance (p < 0.05) in the expanded family collection, with 14q24.1 just falling short (p = 0.055). When we allowed for multiple testing, ten of the 17 nominally significant loci reached the required level of significance (p < 2.8 × 10(-3)). All susceptibility loci had consistent direction of effects with the original study.
  
  
  CONCLUSIONS
  The results for the novel GWA study-identified loci are genuine and not due to population stratification. The next step, namely correlation of the most disease-associated genotypes with phenotypes, such as RNA and protein expression analyses for the candidate genes within or near each of the susceptibility regions, can now proceed.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK. jason.cooper@cimr.cam.ac.uk
authors.forename: J D
authors.initials: JD
authors.lastname: Cooper
authors.forename: J M M
authors.initials: JM
authors.lastname: Howson
authors.forename: D
authors.initials: D
authors.lastname: Smyth
authors.forename: N M
authors.initials: NM
authors.lastname: Walker
authors.forename: H
authors.initials: H
authors.lastname: Stevens
authors.forename: J H M
authors.initials: JH
authors.lastname: Yang
authors.forename: J-X
authors.initials: JX
authors.lastname: She
authors.forename: G S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: M
authors.initials: M
authors.lastname: Rewers
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
authors.forename: B
authors.initials: B
authors.lastname: Akolkar
authors.forename: P
authors.initials: P
authors.lastname: Concannon
authors.forename: H A
authors.initials: HA
authors.lastname: Erlich
authors.forename: C
authors.initials: C
authors.lastname: Julier
authors.forename: G
authors.initials: G
authors.lastname: Morahan
authors.forename: J
authors.initials: J
authors.lastname: Nerup
authors.forename: C
authors.initials: C
authors.lastname: Nierras
authors.forename: F
authors.initials: F
authors.lastname: Pociot
authors.forename: S S
authors.initials: SS
authors.lastname: Rich
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*