Open Access Highly Accessed Research article

A novel serogenetic approach determines the community prevalence of celiac disease and informs improved diagnostic pathways

Robert P Anderson1234*, Margaret J Henry5, Roberta Taylor6, Emma L Duncan78, Patrick Danoy127, Marylia J Costa12, Kathryn Addison7, Jason A Tye-Din123, Mark A Kotowicz59, Ross E Knight10, Wendy Pollock6, Geoffrey C Nicholson118, Ban-Hock Toh6, Matthew A Brown7 and Julie A Pasco59

Author Affiliations

1 The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia

2 Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia

3 Department of Gastroenterology, The Royal Melbourne Hospital, Melbourne Health, Grattan St, Parkville, Victoria 3050, Australia

4 Current address: ImmusanT, Inc., ImmusanT Inc., One Kendall Square, Building 200, LL, Suite 4, Cambridge, MA 02139, USA

5 School of Medicine, Deakin University, Geelong, Victoria, Australia

6 Healthscope Pathology, Melbourne, Victoria, Australia

7 Human Genetics Group, University of Queensland Diamantina Institute, Level 5, Translational Research Institute, 37 Kent St, Woolloongabba, QLD 4102, Australia

8 Endocrinology, Royal Brisbane and Women’s Hospital, Butterfield Rd, Herston, QLD 4029, Australia

9 NorthWest Academic Centre, Department of Medicine, The University of Melbourne, St Albans, Victoria, Australia

10 Geelong Gastroenterology, Level 1, 83 Myers St, Geelong, Victoria 3220, Australia

11 Rural Clinical School, School of Medicine, The University of Queensland, Toowoomba, QLD 4350, Australia

12 Current address: Roche Diagnostics Australia, 31 Victoria Avenue, Castle Hill, New South Wales 2154, Australia

For all author emails, please log on.

BMC Medicine 2013, 11:188  doi:10.1186/1741-7015-11-188

Published: 28 August 2013



Changing perspectives on the natural history of celiac disease (CD), new serology and genetic tests, and amended histological criteria for diagnosis cast doubt on past prevalence estimates for CD. We set out to establish a more accurate prevalence estimate for CD using a novel serogenetic approach.


The human leukocyte antigen (HLA)-DQ genotype was determined in 356 patients with ‘biopsy-confirmed’ CD, and in two age-stratified, randomly selected community cohorts of 1,390 women and 1,158 men. Sera were screened for CD-specific serology.


Only five ‘biopsy-confirmed’ patients with CD did not possess the susceptibility alleles HLA-DQ2.5, DQ8, or DQ2.2, and four of these were misdiagnoses. HLA-DQ2.5, DQ8, or DQ2.2 was present in 56% of all women and men in the community cohorts. Transglutaminase (TG)-2 IgA and composite TG2/deamidated gliadin peptide (DGP) IgA/IgG were abnormal in 4.6% and 5.6%, respectively, of the community women and 6.9% and 6.9%, respectively, of the community men, but in the screen-positive group, only 71% and 75%, respectively, of women and 65% and 63%, respectively, of men possessed HLA-DQ2.5, DQ8, or DQ2.2. Medical review was possible for 41% of seropositive women and 50% of seropositive men, and led to biopsy-confirmed CD in 10 women (0.7%) and 6 men (0.5%), but based on relative risk for HLA-DQ2.5, DQ8, or DQ2.2 in all TG2 IgA or TG2/DGP IgA/IgG screen-positive subjects, CD affected 1.3% or 1.9%, respectively, of females and 1.3% or 1.2%, respectively, of men. Serogenetic data from these community cohorts indicated that testing screen positives for HLA-DQ, or carrying out HLA-DQ and further serology, could have reduced unnecessary gastroscopies due to false-positive serology by at least 40% and by over 70%, respectively.


Screening with TG2 IgA serology and requiring biopsy confirmation caused the community prevalence of CD to be substantially underestimated. Testing for HLA-DQ genes and confirmatory serology could reduce the numbers of unnecessary gastroscopies.

Celiac disease; Diagnosis; Epidemiology; Serology; Transglutaminase; Deamidated gliadin peptide; Immunogenetics; Prevalence