PMID- 15022312
OWN - NLM
STAT- MEDLINE
DCOM- 20040409
LR  - 20161124
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 50
IP  - 3
DP  - 2004 Mar
TI  - Investigation of susceptibility loci identified in the UK rheumatoid arthritis 
      whole-genome scan in a further series of 217 UK affected sibling pairs.
PG  - 729-35
AB  - OBJECTIVE: A previous whole-genome scan (WGS) of 182 UK rheumatoid arthritis (RA) 
      affected sibling pair (ASP) families suggested linkage to HLA and 11 other 
      chromosome regions. Replication of such findings in an independent cohort can 
      help to distinguish true linkages from false-positive linkages. Since RA is a 
      heterogeneous disease, some loci may be linked only in subsets of patients. Thus, 
      the aim of this study was to investigate in an additional set of RA ASP families 
      linkage to regions showing deviation in expected allele-sharing ratios in the UK 
      WGS and to perform subset analysis on the combined cohort. METHODS: Twenty loci 
      were investigated for linkage in 217 Caucasian UK RA ASPs. Stratification 
      analysis was performed on the combined cohort of 377 RA ASP families to account 
      for sex, RA severity, and the shared epitope (SE). RESULTS: None of the regions 
      of linkage identified in the initial WGS achieved statistical significance in the 
      second cohort. In contrast, after stratification analysis, 14 regions showed 
      nominal evidence of linkage (logarithm of odds score >0.8) in one or more 
      subgroups. In particular, the strength of evidence for linkage to chromosome 16p 
      was increased in subsets of ASPs with younger age at disease onset (LOD score 
      2.38) and for linkage to chromosome 6q in female-female ASPs (LOD score 2.31) and 
      in ASPs in which both siblings had 2 copies of the SE (LOD score 3.03). 
      CONCLUSION: These results support the evidence for heterogeneity of RA. This 
      information will inform the future design of association-based investigations as 
      the search for disease genes in the linked regions begins.
FAU - Eyre, Stephen
AU  - Eyre S
AD  - Arthritis Research Campaign Epidemiology Unit, University of Manchester, 
      Manchester, UK.
FAU - Barton, Anne
AU  - Barton A
FAU - Shephard, Neil
AU  - Shephard N
FAU - Hinks, Anne
AU  - Hinks A
FAU - Brintnell, William
AU  - Brintnell W
FAU - MacKay, Kirsten
AU  - MacKay K
FAU - Silman, Alan
AU  - Silman A
FAU - Ollier, William
AU  - Ollier W
FAU - Wordsworth, Paul
AU  - Wordsworth P
FAU - John, Sally
AU  - John S
FAU - Worthington, Jane
AU  - Worthington J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (HLA-DR Antigens)
RN  - 0 (HLA-DRB1 Chains)
SB  - IM
MH  - Age of Onset
MH  - Aged
MH  - Arthritis, Rheumatoid/epidemiology/*genetics
MH  - *Chromosome Mapping
MH  - Chromosomes, Human, Pair 16/genetics
MH  - Chromosomes, Human, Pair 6/genetics
MH  - Cohort Studies
MH  - Female
MH  - Genetic Linkage
MH  - Genetic Predisposition to Disease/*genetics
MH  - *Genome, Human
MH  - HLA-DR Antigens/genetics
MH  - HLA-DRB1 Chains
MH  - Humans
MH  - Lod Score
MH  - Major Histocompatibility Complex/genetics
MH  - Male
MH  - Microsatellite Repeats
MH  - Middle Aged
MH  - Sex Characteristics
MH  - *Siblings
MH  - United Kingdom
EDAT- 2004/03/17 05:00
MHDA- 2004/04/10 05:00
CRDT- 2004/03/17 05:00
PHST- 2004/03/17 05:00 [pubmed]
PHST- 2004/04/10 05:00 [medline]
PHST- 2004/03/17 05:00 [entrez]
AID - 10.1002/art.20039 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2004 Mar;50(3):729-35. doi: 10.1002/art.20039.