title: Contribution of the MHC region to the familial risk of coeliac disease.
abstract: Susceptibility to coeliac disease is genetically determined by possession of specific HLA-DQ alleles, acting in concert with one or more non-HLA linked genes. The pattern of risk seen in sibs and twins in coeliac disease is most parsimonious with a multiplicative model for the interaction between the two classes of genes. Based on a sib recurrence risk for coeliac disease of 10% and a population prevalence of 0.0033, the sib relative risk is 30. To evaluate the contribution of the MHC region to the familial risk of coeliac disease, we have examined haplotype sharing probabilities across this region in 55 coeliac disease families. Based on these probabilities the sib relative risk of coeliac disease associated with the MHC region is 3.7. Combining these results with published data on allele sharing at HLA, the estimated sib relative risk associated with the MHC region is 3.3. Therefore, the MHC genes contribute no more than 40% of the sib familial risk of coeliac disease and the non-HLA linked gene (or genes) are likely to be the stronger determinant of coeliac disease susceptibility.
authors.affiliation: Section of Cancer Genetics, Institute of Cancer Research, Sutton, Surrey.
authors.forename: S
authors.initials: S
authors.lastname: Bevan
authors.forename: S
authors.initials: S
authors.lastname: Popat
authors.forename: C P
authors.initials: CP
authors.lastname: Braegger
authors.forename: A
authors.initials: A
authors.lastname: Busch
authors.forename: D
authors.initials: D
authors.lastname: O'Donoghue
authors.forename: K
authors.initials: K
authors.lastname: Falth-Magnusson
authors.forename: A
authors.initials: A
authors.lastname: Ferguson
authors.forename: A
authors.initials: A
authors.lastname: Godkin
authors.forename: L
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authors.lastname: Hogberg
authors.forename: G
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authors.lastname: Holmes
authors.forename: K B
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authors.lastname: Hosie
authors.forename: P D
authors.initials: PD
authors.lastname: Howdle
authors.forename: H
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authors.lastname: Jenkins
authors.forename: D
authors.initials: D
authors.lastname: Jewell
authors.forename: S
authors.initials: S
authors.lastname: Johnston
authors.forename: N P
authors.initials: NP
authors.lastname: Kennedy
authors.forename: G
authors.initials: G
authors.lastname: Kerr
authors.forename: P
authors.initials: P
authors.lastname: Kumar
authors.forename: R F
authors.initials: RF
authors.lastname: Logan
authors.forename: A H
authors.initials: AH
authors.lastname: Love
authors.forename: M
authors.initials: M
authors.lastname: Marsh
authors.forename: C J
authors.initials: CJ
authors.lastname: Mulder
authors.forename: K
authors.initials: K
authors.lastname: Sjoberg
authors.forename: L
authors.initials: L
authors.lastname: Stenhammer
authors.forename: J
authors.initials: J
authors.lastname: Walker-Smith
authors.forename: A M
authors.initials: AM
authors.lastname: Marossy
authors.forename: R S
authors.initials: RS
authors.lastname: Houlston
mesh_terms: D002446:Celiac Disease / Q000235:genetics*; D005260:Female; D006680:HLA Antigens / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D008285:Major Histocompatibility Complex; D008297:Male; D018570:Risk Assessment
chemical_list: D006680:HLA Antigens