Genetics in twins with Crohn's disease: Less pronounced than previously believed?

Background: The influence of genetics in inflammatory bowel disease is emphasized by twin concordance. Previous studies have methodological limitations. The aims were to establish reliable concordance rates and compare phenotypic characteristics in concordant and discordant monozygotic pairs, anticipating the former reflects a genetically determined subgroup. Methods: By re‐running the Swedish twin registry with the Swedish hospital discharge register, observation time was extended. Diagnoses and phenotype were based on medical notes. Pairs with unknown zygosity and where both twins were not alive or not responding to the questionnaire were excluded. In all, 149 new twin pairs of the same sex, born 1909–1980 were identified. Results: Of new pairs, 4/29 monozygotic, 0/38 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant for Crohn's disease (CD). In ulcerative colitis (UC), 4/31 monozygotic, 4/48 dizygotic, and 0/1 twin pairs with unknown zygosity were concordant. New pairs were added to the original cohort. Restricting analyses to pairs born 1886–1958, the time period used in the original cohort, 9/33 monozygotic and 1/50 dizygotic pairs were concordant for CD (P = 0.008), 6/41 and 3/49, correspondingly, for UC (P = 0.29). There was a trend for concordant twins to have less colonic CD than discordant twins, 15% versus 35% (P = 0.09) in twins born 1886–1980. Conclusions: Previous twin studies have overestimated the influence of genetics in CD. A trend for phenotypic difference between concordant and discordant pairs was observed, suggesting that the clinical entity represents diseases with different pathophysiological backgrounds. (Inflamm Bowel Dis 2011;)

[1]  M. Vatn,et al.  Clinical course during the first 10 years of ulcerative colitis: results from a population-based inception cohort (IBSEN Study) , 2009, Scandinavian journal of gastroenterology.

[2]  M. Spehlmann,et al.  Epidemiology of inflammatory bowel disease in a German twin cohort: Results of a nationwide study , 2008, Inflammatory bowel diseases.

[3]  L. Bodin,et al.  Longitudinal concordance for clinical characteristics in a Swedish‐Danish twin population with inflammatory bowel disease , 2007, Inflammatory bowel diseases.

[4]  M. Vatn,et al.  Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. , 2007, Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association.

[5]  R. Sartor.  Mechanisms of Disease: pathogenesis of Crohn's disease and ulcerative colitis , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[6]  A. Lapidus.  Crohn's disease in Stockholm County during 1990-2001: an epidemiological update. , 2006, World journal of gastroenterology.

[7]  L. Hougs,et al.  Disease Concordance, Zygosity, and NOD2/CARD15 Status: Follow-Up of a Population-Based Cohort of Danish Twins with Inflammatory Bowel Disease , 2005, The American Journal of Gastroenterology.

[8]  J. Satsangi,et al.  Toward an integrated clinical, molecular and serological classification of inflammatory bowel disease: report of a Working Party of the 2005 Montreal World Congress of Gastroenterology. , 2005, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[9]  P. Lakatos,et al.  Selection criteria for preoperative endoscopic retrograde cholangiopancreatography before laparoscopic cholecystectomy and endoscopic treatment of bile duct stones: results of a retrospective, single center study between 1996-2002. , 2004, World journal of gastroenterology.

[10]  P. Lakatos,et al.  Striking elevation in incidence and prevalence of inflammatory bowel disease in a province of western Hungary between 1977-2001. , 2004, World journal of gastroenterology.

[11]  J. Askling,et al.  Changing pattern of paediatric inflammatory bowel disease in northern Stockholm 1990–2001 , 2003, Gut.

[12]  E. Lindberg,et al.  Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. , 2003, Gastroenterology.

[13]  P. Lichtenstein,et al.  The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies , 2002, Journal of internal medicine.

[14]  T. Ahmad,et al.  The molecular classification of the clinical manifestations of Crohn's disease. , 2002, Gastroenterology.

[15]  T. Sørensen,et al.  Concordance of inflammatory bowel disease among Danish twins. Results of a nationwide study. , 2000, Scandinavian journal of gastroenterology.

[16]  O Bernell,et al.  Risk factors for surgery and postoperative recurrence in Crohn's disease. , 2000, Annals of surgery.

[17]  R. Pounder,et al.  Concordance rates of twins and siblings in inflammatory bowel disease (IBD) , 1998 .

[18]  R. Löfberg,et al.  Incidence of Crohn’s disease in Stockholm County 1955–1989 , 1997, Gut.

[19]  P. Rutgeerts,et al.  Familial aggregation in Crohn's disease: increased age-adjusted risk and concordance in clinical characteristics. , 1996, Gastroenterology.

[20]  R. Pounder,et al.  Genetics versus environment in inflammatory bowel disease: results of a British twin study , 1996, BMJ.

[21]  P. Munkholm,et al.  Disease activity courses in a regional cohort of Crohn's disease patients. , 1995, Scandinavian journal of gastroenterology.

[22]  P. Munkholm,et al.  Course of ulcerative colitis: analysis of changes in disease activity over years. , 1994, Gastroenterology.

[23]  S. Targan,et al.  Familial empirical risks for inflammatory bowel disease: differences between Jews and non-Jews. , 1993, Gut.

[24]  G. Hellers,et al.  Prevalence of inflammatory bowel disease among relatives of patients with Crohn's disease. , 1991, Scandinavian journal of gastroenterology.

[25]  C. Leijonmarck,et al.  Factors affecting colectomy rate in ulcerative colitis: an epidemiologic study. , 1990, Gut.

[26]  J. Lennard-jones,et al.  Classification of inflammatory bowel disease. , 1989, Scandinavian journal of gastroenterology. Supplement.

[27]  E. Lindberg,et al.  Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking. , 1988, Gut.