Presence of high-risk HLA genotype is the most important individual risk factor for coeliac disease among at-risk relatives

Saana Paavola, Katri Lindfors, Laura Kivelä, Juliana Cerqueira, Heini Huhtala, Päivi Saavalainen, Riku Tauschi, Katri Kaukinen, Kalle Kurppa

Research output: Contribution to journalArticleScientificpeer-review

4 Downloads (Pure)


Background: Family screening has been advocated as a means to reduce the major underdiagnosis of coeliac disease. However, the precise risk of the disease in relatives and the impact of patient- and relative-related individual factors remain obscure. Aims: To investigate the individual risk of coeliac disease among patients' relatives. Methods: Altogether 2943 relatives of 624 index patients were assessed for the presence of previous coeliac disease diagnosis, or were screened for the disease. Coeliac disease-associated human leucocyte antigen (HLA) genotype was determined from all participants. The association between individual factors and new screening positivity was assessed by logistic regression. Results: There were 229 previously diagnosed non-index relatives with coeliac disease and 2714 non-affected (2067 first-degree, 647 more distant) relatives. Of these 2714 relatives, 129 (4.8%) were screening-positive (first-degree 5.1%, second-degree 3.6%, more distant 3.5%). The combined prevalence of the previously diagnosed and now detected cases in relatives was 12.2% (6.3% clinically detected, 5.9% screen-detected). In univariate analysis, age <18 years at diagnosis (odds ratio 1.60, 95% CI 1.04-2.45) in index, and age 41-60 years (1.73, 1.10-2.73), being a sibling (1.65, 1.06-2.59) and having the high-risk genotype (3.22, 2.01-5.15 DQ2.5/2.5 or DQ2.5/2.2 vs other risk alleles) in relatives were associated with screening positivity. Only high-risk HLA remained significant (2.94, 1.80-4.78) in multivariable analysis. Conclusions: Unrecognised coeliac disease was common among at-risk relatives even in a country with an active case-finding policy, and also in relatives more distant than first-degree. The presence of a high-risk genotype was the most important predictor for screening positivity. identifier NCT03136731.

Original languageEnglish
JournalAlimentary Pharmacology and Therapeutics
Issue number6
Publication statusPublished - 2021
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 2

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology
  • Pharmacology (medical)


Dive into the research topics of 'Presence of high-risk HLA genotype is the most important individual risk factor for coeliac disease among at-risk relatives'. Together they form a unique fingerprint.

Cite this