Autoimmune disease in first-degree relatives and spouses of individuals with celiac disease

Louise Emilsson, Cisca Wijmenga, Joseph A Murray, Jonas F. Ludvigsson

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background & Aims: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. Methods: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n=29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n= 84,648) and controls (n= 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. Results: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P= .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. Conclusions: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.

Original languageEnglish (US)
Pages (from-to)1271-1277
Number of pages7
JournalClinical Gastroenterology and Hepatology
Volume13
Issue number7
DOIs
StatePublished - Jul 1 2015

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Celiac Disease
Spouses
Autoimmune Diseases
Confidence Intervals
Biopsy
Safety Management
Wetlands
Hyperthyroidism
Sarcoidosis
Hypothyroidism
Autoimmunity
Type 1 Diabetes Mellitus
Ulcerative Colitis
Psoriasis
Sweden
Fathers
Crohn Disease
Systemic Lupus Erythematosus
Atrophy
Registries

Keywords

  • Autoimmune
  • Celiac
  • Cohort
  • Genetics
  • Heredity
  • Population study
  • Risk factor
  • Shared genetics

ASJC Scopus subject areas

  • Gastroenterology
  • Hepatology
  • Medicine(all)

Cite this

Autoimmune disease in first-degree relatives and spouses of individuals with celiac disease. / Emilsson, Louise; Wijmenga, Cisca; Murray, Joseph A; Ludvigsson, Jonas F.

In: Clinical Gastroenterology and Hepatology, Vol. 13, No. 7, 01.07.2015, p. 1271-1277.

Research output: Contribution to journalArticle

Emilsson, Louise ; Wijmenga, Cisca ; Murray, Joseph A ; Ludvigsson, Jonas F. / Autoimmune disease in first-degree relatives and spouses of individuals with celiac disease. In: Clinical Gastroenterology and Hepatology. 2015 ; Vol. 13, No. 7. pp. 1271-1277.
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N2 - Background & Aims: First-degree relatives of individuals with celiac disease are at increased risk for this disorder, but little is known about their risk for other autoimmune diseases. We assessed the risk of nonceliac autoimmune disease in first-degree relatives and spouses of people with celiac disease. Methods: We identified individuals with celiac disease by searching computerized duodenal and jejunal biopsies, collected from 1969 through 2008, at 28 pathology departments in Sweden. Celiac disease was identified based on biopsy reports of villous atrophy (equal to Marsh grade 3; n=29,096). Individuals with celiac disease were matched with up to 5 controls (people without celiac disease) for sex, age, county, and calendar year (total, 144,522 controls). Through Swedish health care registries, we identified all first-degree relatives (fathers, mothers, siblings, and offspring) and spouses of individuals with celiac disease (n= 84,648) and controls (n= 430,942). We used Cox regression analysis to calculate hazard ratios (HRs) for nonceliac autoimmune disease (Crohn's disease, type 1 diabetes mellitus, hypothyroidism, hyperthyroidism, psoriasis, rheumatoid arthritis, sarcoidosis, systemic lupus erythematosus, or ulcerative colitis) in these groups. Results: During the follow-up period (median, 10.8 y), 3333 of the first-degree relatives of patients with celiac disease (3.9%) and 12,860 relatives of controls (3.0%) had an autoimmune disease other than celiac disease. First-degree relatives of people with celiac disease were at increased risk of nonceliac autoimmune disease, compared with controls (HR, 1.28; 95% confidence interval, 1.23-1.33), as were spouses (HR, 1.20; 95% confidence interval, 1.06-1.35). Risk estimates for nonceliac autoimmune disease did not differ between first-degree relatives and spouses of individuals with celiac disease (interaction test: P= .11). HRs for nonceliac autoimmune disease were highest in the first 2 years of follow-up evaluation. Conclusions: First-degree relatives and spouses of individuals with celiac disease are at increased risk of nonceliac autoimmune disease. In addition to genetic factors, environmental factors and ascertainment bias might contribute to the increased risk of autoimmunity in first-degree relatives of individuals with celiac disease.

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