A common genetic background for inflammatory bowel disease and ankylosing spondylitis: A genealogic study in Iceland

• Published in: Arthritis and rheumatism Vol. 56; no. 8; pp. 2633 - 2639
• Main Authors: Thjodleifsson, Bjarni, Geirsson, árni J., Björnsson, Sigurdur, Bjarnason, Ingvar
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.08.2007; Wiley
• Subjects: Biological and medical sciences; Diseases of the osteoarticular system; Diseases of the spine; Family Health; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genetic Predisposition to Disease; Humans; Iceland - epidemiology; Inflammatory Bowel Diseases - epidemiology; Inflammatory Bowel Diseases - genetics; Inflammatory Bowel Diseases - pathology; Inflammatory joint diseases; Male; Medical sciences; Molecular Epidemiology - methods; Odds Ratio; Other diseases. Semiology; Pedigree; Spondylitis, Ankylosing - epidemiology; Spondylitis, Ankylosing - genetics; Spondylitis, Ankylosing - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Atlantic Ocean Islands; Iceland; Human; Diseases of the osteoarticular system; Inflammatory joint disease; Spine disease; Inflammatory disease; Genetic disease; Spondylarthropathy; Crohn disease; Chronic; Digestive diseases; Intestinal disease; Diagnosis; Ankylosing spondylitis; Ulcerative colitis
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/art.22812

Objective Patients with ankylosing spondylitis (AS) and ∼50% of their first‐degree relatives may have a genetic abnormality that results in subclinical intestinal inflammation. This study was undertaken to examine the familial occurrence and cosegregation of AS and inflammatory bowel disease (IBD) in order to determine whether there is a shared genetic risk factor in families. Methods The Icelandic genealogy database and population‐wide data on all living Icelanders diagnosed as having AS (n = 205) and/or IBD (n = 1,352) were used to estimate the risk ratios of AS for relatives of patients with AS, the risk ratios of IBD for relatives of patients with IBD, and the cross‐risk ratios of AS for relatives of patients with IBD or of IBD for relatives of patients with AS. The mean kinship coefficients for each disease were calculated. The control population for disease risk calculations comprised 10,000–100,000 sets of matched Icelandic subjects. Results First‐, second‐, and third‐degree relatives of patients with AS had risk ratios of 94, 25, and 3.5, respectively, indicating an increased risk of developing AS (each P < 0.0005), while first‐, second‐, and third‐degree relatives of patients with IBD had risk ratios for IBD of 4.4, 2.2, and 1.4, respectively (each P < 0.0001). The cross‐risk ratios of IBD were 3.0 and 2.1 in first‐ and second‐degree relatives of patients with AS, respectively, and were the same for AS in first‐ and second‐degree relatives of patients with IBD. With the exception of Crohn's disease, the risk of having AS, ulcerative colitis, or IBD in spouses of patients with these diseases did not differ significantly from that in controls. Calculation of the kinship coefficients confirmed these patterns of familial risk. Conclusion Patients with AS or IBD in Iceland are significantly more related to each other than are randomly sampled control subjects, in terms of an increased risk of either or both conditions developing in third‐degree relatives. These findings suggest that one or more undiscovered genetic variants may underlie the risk of both diseases.