Clinical-alimentary tractA major non-HLA locus in celiac disease maps to chromosome 191 ☆,
Section snippets
Study subjects
Families with 2 or more siblings affected with celiac disease were invited to participate in our study through an advertisement in the Dutch Celiac Society’s newsletter. Several families were also referred by their medical specialists. Blood was collected from those families in which the affected siblings were diagnosed by a small-bowel biopsy. All biopsy samples on which the original celiac disease diagnosis had been established were collected and sent to an experienced pathologist (J.W.R.M.)
Initial genome-wide screen
Sixty-seven families with 84 affected sibpairs were available for the initial genome-wide screen. Power calculations were performed to estimate the chance to detect susceptibility loci with different relative risks to a sibling of a celiac disease patient (λs). It was estimated that, with this set of families, the chance to detect a locus with a λs of 1.5 was 20%, a λs of 2.0 was 72%, a λs of 2.5 was 94%, and λs of 3.0 was 99%. A whole genome screen with microsatellite markers was performed in
Discussion
Sixty-seven families with affected sibpairs of Dutch ancestry were available for the initial genome-wide screen. A total of 84 affected sibpairs were present in these families. It was shown by power calculations that this dataset had a very high chance of detecting a celiac disease susceptibility locus with a locus-specific λs ≥ 2.5 (>94%). Also, the chance to detect a locus with a λs of 2.0 is still reasonably good (72%). However, this dataset has limited power to detect loci with smaller
Acknowledgements
The authors thank the Dutch Celiac Disease Foundation for helping us contact the celiac disease families and to all the families who participated in our study; Arjenne Kors, Anath Oren, and Winny van der Hoeven for collecting the blood samples; Eric Strengman and Ruben van ‘t Slot for isolating the DNA and checking the blind control samples; Lude Franke for blasting the primer sequences; Alienke Monsuur for typing part of the chromosome 6 markers; Bobby Koeleman for statistical advice; Greetje
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Cited by (0)
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Supported by a grant from the Dutch Digestive Diseases Foundation (WS 97-44 to C.W. and R.H.J.H.).
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This study is dedicated to the memory of Lodewijk Sandkuijl (1953–2002), who died shortly after its completion. He was an inspiration to us and was a world expert on biostatistics.
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Deceased.