Genomewide linkage analysis of celiac disease in Finnish families.
Celiac disease (CD), or gluten-sensitive enteropathy, is a common multifactorial disorder resulting from intolerance to cereal prolamins. The only established genetic susceptibility factor is HLA-DQ, which appears to explain only part of the overall genetic risk. We performed a genomewide scan of CD in 60 Finnish families. In addition to strong evidence for linkage to the HLA region at 6p21.3 (Z(max)>5), suggestive evidence for linkage was found for six other chromosomal regions--1p36, 4p15, 5q31, 7q21, 9p21-23, and 16q12. We further analyzed the three most convincing regions--4p15, 5q31, and 7q21--by evaluation of dense marker arrays across each region and by analysis of an additional 38 families. Although multipoint analysis with dense markers provided supportive evidence (multipoint LOD scores 3.25 at 4p15, 1.49 at 5q31, and 1.04 at 7q21) for the initial findings, the additional 38 families did not strengthen evidence for linkage. The role that HLA-DQ plays was studied in more detail by analysis of DQB1 alleles in all 98 families. All but one patient carried one or two HLA-DQ risk alleles, and 65% of HLA-DQ2 carriers were affected. Our study indicates that the HLA region harbors a predominant CD-susceptibility locus in these Finnish families.
Liu
Jianjun
J
Columbia Genome Center, Columbia University, New York, NY, USA.
Juo
Suh-Hang
SH
Holopainen
Päivi
P
Terwilliger
Joseph
J
Tong
Xiaomei
X
Grunn
Adina
A
Brito
Miguel
M
Green
Peter
P
Mustalahti
Kirsi
K
Mäki
Markku
M
Gilliam
T Conrad
TC
Partanen
Jukka
J
D000328:Adult; D000483:Alleles; D002446:Celiac Disease / Q000235:genetics*; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D005387:Finland; D005787:Gene Frequency / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006801:Humans; D008126:Lod Score
D005819:Genetic Markers; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen