BACKGROUND AND AIMS: The pathogenesis of celiac disease is still unknown despite its well-known association with human leukocyte antigen (HLA)-DQ2 and DQ8. It is clear that non-HLA genes contribute to celiac disease development as well, but none of the previous genome-wide screens in celiac disease have resulted in identification of these genes. METHODS: We, therefore, performed a 2-stage, genome-wide screen in 101 affected sibpairs from 82 Dutch families who met strict diagnostic criteria. The small intestinal biopsy samples, on which the original celiac disease diagnoses had been based, showed a Marsh III lesion in all patients on reevaluation by 1 pathologist. For association analysis of markers in regions linked to celiac disease, 216 independent MIII patients and 216 age- and sex-matched controls were available. RESULTS: As expected, highly significant linkage to the HLA-region was detected (multipoint maximum lod score [MMLS] = 8.14). More importantly, significant linkage was also present at 19p13.1 (MMLS = 4.31), with the peak at marker D19S899. Moreover, this marker was also significantly associated with celiac disease in the case-control study (corrected P = 0.016). Furthermore, we identified suggestive linkage to 6q21-22, which is approximately 70 cM downstream from the HLA region (MMLS = 3.10). CONCLUSIONS: Significant linkage of celiac disease to chromosome region 19p13.1 was detected in our genome-wide screen. These results were confirmed by the association of D19S899 to celiac disease in an independent case-control cohort. Furthermore, we identified a possible second celiac disease locus on chromosome region 6q21-22.
BACKGROUND AND AIMS: The pathogenesis of celiac disease is still unknown despite its well-known association with human leukocyte antigen (HLA)-DQ2 and DQ8. It is clear that non-HLA genes contribute to celiac disease development as well, but none of the previous genome-wide screens in celiac disease have resulted in identification of these genes. METHODS: We, therefore, performed a 2-stage, genome-wide screen in 101 affected sibpairs from 82 Dutch families who met strict diagnostic criteria. The small intestinal biopsy samples, on which the original celiac disease diagnoses had been based, showed a Marsh III lesion in all patients on reevaluation by 1 pathologist. For association analysis of markers in regions linked to celiac disease, 216 independent MIII patients and 216 age- and sex-matched controls were available. RESULTS: As expected, highly significant linkage to the HLA-region was detected (multipoint maximum lod score [MMLS] = 8.14). More importantly, significant linkage was also present at 19p13.1 (MMLS = 4.31), with the peak at marker D19S899. Moreover, this marker was also significantly associated with celiac disease in the case-control study (corrected P = 0.016). Furthermore, we identified suggestive linkage to 6q21-22, which is approximately 70 cM downstream from the HLA region (MMLS = 3.10). CONCLUSIONS: Significant linkage of celiac disease to chromosome region 19p13.1 was detected in our genome-wide screen. These results were confirmed by the association of D19S899 to celiac disease in an independent case-control cohort. Furthermore, we identified a possible second celiac disease locus on chromosome region 6q21-22.
Authors: Paola Forabosco; Susan L Neuhausen; Luigi Greco; Asa Torinsson Naluai; Cisca Wijmenga; Paivi Saavalainen; Richard S Houlston; Paul J Ciclitira; Marie-Claude Babron; Cathryn M Lewis Journal: Hum Hered Date: 2009-07-22 Impact factor: 0.444
Authors: Elisabet Einarsdottir; Marianna R Bevova; Alexandra Zhernakova; Alienke Monsuur; Lotta L E Koskinen; Ruben van't Slot; Chris Mulder; M Luisa Mearin; Ilma R Korponay-Szabo; Katri Kaukinen; Kalle Kurppa; Juha Kere; Markku Mäki; Cisca Wijmenga; Päivi Saavalainen Journal: Eur J Hum Genet Date: 2011-02-16 Impact factor: 4.246
Authors: Alexandra Zhernakova; Peter Eerligh; Pilar Barrera; Joanna Z Wesoly; Joanna Z Weseloy; Tom W J Huizinga; Bart O Roep; Cisca Wijmenga; Bobby P C Koeleman Journal: Hum Genet Date: 2005-07-16 Impact factor: 4.132
Authors: C Núñez; B Rueda; A Martínez; C Maluenda; I Polanco; M-A López-Nevot; E Ortega; E Sierra; E Gómez de la Concha; E Urcelay; J Martín Journal: World J Gastroenterol Date: 2006-07-21 Impact factor: 5.742