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Dense Genotyping Pinpoints Numerous Common and Rare Variant Association Signals in Celiac Disease

Celiac.com 02/22/2012 - A research team recently conducted a dense genotyping non-HLA risk loci previously associated with immune-mediated diseases in individuals with celiac disease. The study was conducted under the auspices of the Genetics Department, University Medical Center and University of Groningen, The Netherlands.

Photo: CC-Bogdan SudituThe team used variants from the 1000 Genomes Project pilot European CEU dataset, along with data from additional re-sequencing studies, to densely genotype a total of 183 non-HLA risk loci previously associated with immune-mediated diseases in 12,041 individuals with celiac disease and in 12,228 control subjects.

They were able to discover thirteen new celiac disease risk loci reaching genome-wide significance. This discovery brings the number of loci known to be associated with celiac disease, including the HLA locus, to forty.

The team found multiple independent association signals in more than one in three of the loci. This is likely due to a combination of common, low-frequency and rare genetic variants.

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Compared to earlier data, such as those from HapMap3, the large study group and the dense gene mapping made for a much higher resolution of the pattern of linkage disequilibrium and suggested localization of many signals to finer scale regions.

In all, the team found that 29 of the 54 fine-mapped signals seemed to be localized to single genes and, in some instances, to gene regulatory elements.

Finally, they defined the complex genetic architecture of the risk regions of celiac disease. They also refined the risk signals for celiac disease, which provide support for the next steps in understanding its causes.

The research team included G. Trynka, K. A. Hunt, N. A. Bockett, J. Romanos, V. Mistry, A. Szperl, S. F. Bakker, M. T. Bardella, L. Bhaw-Rosun, G. Castillejo, E. G. de la Concha, R. C. de Almeida, K. R. Dias, C. C. van Diemen, P.C. Dubois, R. H. Duerr, S. Edkins, L. Franke, K. Fransen, J. Gutierrez, G. A. Heap, B. Hrdlickova, S. Hunt, L. P. Izurieta, V. Izzo, L. A. Joosten, C. Langford, M. C. Mazzilli, C. A. Mein, V. Midah, M. Mitrovic, B. Mora, M. Morelli, S. Nutland, C. Núñez, S. Onengut-Gumuscu, K. Pearce, M. Platteel, I. Polanco, S. Potter, C. Ribes-Koninckx, I. Ricaño-Ponce, S. S. Rich, A. Rybak, J. L. Santiago, S. Senapati, A. Sood, H. Szajewska, R. Troncone, J. Varadé, C. Wallace, V. M. Wolters, and A. Zhernakova. The study team also included B. K. Thelma, B. Cukrowska, E. Urcelay, J. R. Bilbao, M. L. Mearin, D. Barisani, J. C. Barrett, V. Plagnol, P. Deloukas, C. Wijmenga, and D. A. van Heel, who are variously affiliated with the Spanish Consortium on the Genetics of Coeliac Disease (CEGEC), the PreventCD Study Group, and the Wellcome Trust Case Control Consortium (WTCCC).

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check out CoQ10, not related to celiac (as far as I know) but for balance issues.

remind your hubby, "if mama ain't happy, ain't nobody gonna be happy."

Thank you for all your help with this. I was also wondering if I could ask and hope you don't mind, will they be able to tell Celiac on the camera or will it be down to the biopsies they take? My endoscopy is on the 9th, and I am worried about not having enough gluten to show.

Vegetarian here too, celiac really makes it tough as all the Quorn meat replacement products bar the odd one or two are out Then there's all the scare sites saying only paleo type diets will repair your insides but guess what they're all heavily meat / fish based. @Ennis_TX has some good ideas for meals

Wow guys just read all the replies Thankyou all so much!!! There are so many things you've all said that has triggered a light bulb in my little head! The glasses may not be clean!! I will put this to a test. One night I'll stick to bottles of cider (double checked are gluten-free) another I'll try the Gin or William chase vodka if I can find it! And see the effects. if I loose many days due to these not working I'll see a practitioner and see what the deal is! Before I was diagnosed at Coeliac... I went to a herbalist who did a test and said corn is funny on my body!!! But then 18months later (when I became incontinant and lost a lot of weight) my bloods came back positive (after begging the docs and telling them it wasn't IBS) i don't tend to snack at bars on food but I must admit I never thought it could be the way it's served!! The humour and information has made me feel so much better thanks all xxx