title: Whole-genome linkage analysis of rheumatoid arthritis susceptibility loci in 252 affected sibling pairs in the United Kingdom.
abstract: OBJECTIVE
  To undertake a systematic whole-genome screen to identify regions exhibiting genetic linkage to rheumatoid arthritis (RA).
  
  
  METHODS
  Two hundred fifty-two RA-affected sibling pairs from 182 UK families were genotyped using 365 highly informative microsatellite markers. Microsatellite genotyping was performed using fluorescent polymerase chain reaction primers and semiautomated DNA sequencing technology. Linkage analysis was undertaken using MAPMAKER/SIBS for single-point and multipoint analysis.
  
  
  RESULTS
  Significant linkage (maximum logarithm of odds score 4.7 [P = 0.000003] at marker D6S276, 1 cM from HLA-DRB1) was identified around the major histocompatibility complex (MHC) region on chromosome 6. Suggestive linkage (P < 7.4 x 10(-4)) was identified on chromosome 6q by single- and multipoint analysis. Ten other sites of nominal linkage (P < 0.05) were identified on chromosomes 3p, 4q, 7p, 2 regions of 10q, 2 regions of 14q, 16p, 21q, and Xq by single-point analysis and on 3 sites (1q, 14q, and 14q) by multipoint analysis.
  
  
  CONCLUSIONS
  Linkage to the MHC region was confirmed. Eleven non-HLA regions demonstrated evidence of suggestive or nominal linkage, but none reached the genome-wide threshold for significant linkage (P = 2.2 x 10(-5)). Results of previous genome screens have suggested that 6 of these regions may be involved in RA susceptibility.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, UK. Jane@fs1.ser.man.ac.uk
authors.forename: Kirsten
authors.initials: K
authors.lastname: MacKay
authors.forename: Stephen
authors.initials: S
authors.lastname: Eyre
authors.forename: Anne
authors.initials: A
authors.lastname: Myerscough
authors.forename: Anita
authors.initials: A
authors.lastname: Milicic
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Steven
authors.initials: S
authors.lastname: Laval
authors.forename: Jenny
authors.initials: J
authors.lastname: Barrett
authors.forename: Dorothea
authors.initials: D
authors.lastname: Lee
authors.forename: Sarah
authors.initials: S
authors.lastname: White
authors.forename: Sally
authors.initials: S
authors.lastname: John
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Bell
authors.forename: Alan
authors.initials: A
authors.lastname: Silman
authors.forename: William
authors.initials: W
authors.lastname: Ollier
authors.forename: Paul
authors.initials: P
authors.lastname: Wordsworth
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002874:Chromosome Mapping; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D016678:Genome; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics; D018895:Microsatellite Repeats; D009679:Nuclear Family; D015588:Observer Variation; D006113:United Kingdom