| Title: | A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease: a pilot study in clinical care |
| Journal: | Alimentary Pharmacology & Therapeutics |
| Published: | 13 Aug 2020 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/32790217/ |
| DOI: | https://doi.org/10.1111/apt.15826 |
| URL: | https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/apt.15826 |
| Citations: | 18 (5 in last 2 years) as of 8 Aug 2024 |
Publication 3947
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Abstract
BACKGROUND: Single nucleotide polymorphism-based genetic risk scores (GRS) model genetic risk as a continuum and can discriminate coeliac disease but have not been validated in clinic. Human leukocyte antigen (HLA) DQ gene testing is available in clinic but does not include non-HLA attributed risk and is limited by discrete risk stratification.</p>
AIMS: To accurately characterise both HLA and non-HLA coeliac disease genetic risk as a single nucleotide polymorphism-based GRS and evaluate diagnostic utility.</p>
METHODS: We developed a 42 single nucleotide polymorphism coeliac disease GRS from a European case-control study (12 041 cases vs 12 228 controls) using HLA-DQ imputation and published genome-wide association studies. We validated the GRS in UK Biobank (1237 cases) and developed direct genotyping assays. We tested the coeliac disease GRS in a pilot clinical cohort of 128 children presenting with suspected coeliac disease.</p>
RESULTS: The GRS was more discriminative of coeliac disease than HLA-DQ stratification in UK Biobank (receiver operating characteristic area under the curve [ROC-AUC] = 0.88 [95% CIs: 0.87-0.89] vs 0.82 [95% CIs: 0.80-0.83]). We demonstrated similar discrimination in the pilot clinical cohort (114 cases vs 40 controls, ROC-AUC = 0.84 [95% CIs: 0.76-0.91]). As a rule-out test, no children with coeliac disease in the clinical cohort had a GRS below 38th population centile.</p>
CONCLUSIONS: A single nucleotide polymorphism-based GRS may offer more effective and cost-efficient testing of coeliac disease genetic risk in comparison to HLA-DQ stratification. As a comparatively inexpensive test it could facilitate non-invasive coeliac disease diagnosis but needs detailed assessment in the context of other diagnostic tests and against current diagnostic algorithms.</p>
8 Keywords
- Case-Control Studies
- Celiac Disease
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Pilot Projects
- Polymorphism, Single Nucleotide
- Risk Factors
13 Authors
- Seth A. Sharp
- Samuel E. Jones
- Robert A. Kimmitt
- Michael N. Weedon
- Anne M. Halpin
- Andrew R. Wood
- Robin N. Beaumont
- Seema King
- David A. van Heel
- Patricia M. Campbell
- William A. Hagopian
- Justine M. Turner
- Richard A Oram
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