Whole-genome screening in ankylosing spondylitis: Evidence of non-MHC genetic-susceptibility loci

被引:198
作者
Laval, SH
Timms, A
Edwards, S
Bradbury, L
Brophy, S
Milicic, A
Rubin, L
Siminovitch, KA
Weeks, DE
Calin, A
Wordsworth, BP
Brown, MA
机构
[1] Wellcome Trust Ctr Human Genet, Spondyloarthrit & Bone Dis Res Grp, Headington OX3 7BN, England
[2] Royal Natl Hosp Rheumat Dis, Bath BA1 1RL, Avon, England
[3] St Michaels Hosp, Div Rheumatol, Toronto, ON M5B 1W8, Canada
[4] Univ Toronto, Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada
[5] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA
基金
英国医学研究理事会;
关键词
D O I
10.1086/319509
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonparametric linkage analysis was performed. Regions were identified showing "suggestive" or stronger linkage with the disease on chromosomes 1p, 2q, 6p, 9q, 10q, 16q, and 19q. The MHC locus was identified as encoding the greatest component of susceptibility, with an overall LOD score of 15.6. The strongest non-MHC linkage lies on chromosome 16q (overall LOD score 4.7). These results strongly support the presence of non-MHC genetic-susceptibility factors in AS and point to their likely locations.
引用
收藏
页码:918 / 926
页数:9
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