A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease : a pilot study in clinical care
© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd..
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.
AIMS: To accurately characterise both HLA and non-HLA coeliac disease genetic risk as a single nucleotide polymorphism-based GRS and evaluate diagnostic utility.
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.
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.
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.
| Errataetall: |
CommentIn: Aliment Pharmacol Ther. 2021 Mar;53(6):759-760. - PMID 33599319 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:52 |
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| Enthalten in: |
Alimentary pharmacology & therapeutics - 52(2020), 7 vom: 05. Okt., Seite 1165-1173 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sharp, Seth A [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 11.01.2021 Date Revised 30.03.2021 published: Print-Electronic CommentIn: Aliment Pharmacol Ther. 2021 Mar;53(6):759-760. - PMID 33599319 Citation Status MEDLINE |
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| doi: |
10.1111/apt.15826 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313649243 |
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| 100 | 1 | |a Sharp, Seth A |e verfasserin |4 aut | |
| 245 | 1 | 2 | |a A single nucleotide polymorphism genetic risk score to aid diagnosis of coeliac disease |b a pilot study in clinical care |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Completed 11.01.2021 | ||
| 500 | |a Date Revised 30.03.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a CommentIn: Aliment Pharmacol Ther. 2021 Mar;53(6):759-760. - PMID 33599319 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd. | ||
| 520 | |a 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 | ||
| 520 | |a AIMS: To accurately characterise both HLA and non-HLA coeliac disease genetic risk as a single nucleotide polymorphism-based GRS and evaluate diagnostic utility | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 700 | 1 | |a Jones, Samuel E |e verfasserin |4 aut | |
| 700 | 1 | |a Kimmitt, Robert A |e verfasserin |4 aut | |
| 700 | 1 | |a Weedon, Michael N |e verfasserin |4 aut | |
| 700 | 1 | |a Halpin, Anne M |e verfasserin |4 aut | |
| 700 | 1 | |a Wood, Andrew R |e verfasserin |4 aut | |
| 700 | 1 | |a Beaumont, Robin N |e verfasserin |4 aut | |
| 700 | 1 | |a King, Seema |e verfasserin |4 aut | |
| 700 | 1 | |a van Heel, David A |e verfasserin |4 aut | |
| 700 | 1 | |a Campbell, Patricia M |e verfasserin |4 aut | |
| 700 | 1 | |a Hagopian, William A |e verfasserin |4 aut | |
| 700 | 1 | |a Turner, Justine M |e verfasserin |4 aut | |
| 700 | 1 | |a Oram, Richard A |e verfasserin |4 aut | |
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