Increased risk of primary sclerosing cholangitis and ulcerative colitis in first-degree relatives of patients with primary sclerosing cholangitis.
OBJECTIVE
The importance of genetic factors for the development of primary sclerosing cholangitis (PSC) is incompletely understood. This study assessed the risk of PSC and inflammatory bowel disease (IBD) among first-degree relatives of patients with PSC, compared with the first-degree relatives of a cohort without PSC.


METHODS
Subjects from the national Swedish cohort of PSC patients (n = 678) were matched for date of birth, sex, and region to up to 10 subjects without a diagnosis of PSC (n = 6347). Linkage through general population registers identified first-degree relatives of subjects in both the PSC and comparison cohorts (n = 34,092). Diagnoses among first-degree relatives were identified by using the Inpatient Register.


RESULTS
The risk of cholangitis was statistically significantly increased in offspring, siblings, and parents of the PSC patient cohort, compared with relatives of the comparison cohort, with the hazard ratios and 95% confidence intervals, 11.5 (1.6-84.4), 11.1 (3.3-37.8), and 2.3 (0.9-6.1), respectively. The hazard ratios for ulcerative colitis (UC) among first-degree relatives of all PSC patients was 3.3 (2.3-4.9) and for Crohn's disease 1.4 (0.8-2.5). The risk of UC for relatives of PSC patients without IBD was also increased, 7.4 (2.9-18.9).


CONCLUSIONS
First-degree relatives of patients with PSC run an increased risk of PSC, indicating the importance of genetic factors in the etiology of PSC. First-degree relatives of PSC patients without IBD are also at an increased risk of UC, which might indicate shared genetic susceptibility factors for PSC and UC.
Bergquist
Annika
A
Department of Gastroenterology and Hepatology, Karolinska University Hospital, Karolinska Institute, Huddinge and Solna, Stockholm, Sweden. annika.bergquist@ki.se
Montgomery
Scott M
SM
Bahmanyar
Shahram
S
Olsson
Rolf
R
Danielsson
Ake
A
Lindgren
Stefan
S
Prytz
Hanne
H
Hultcrantz
Rolf
R
Lööf
L A R S
LA
Sandberg-Gertzén
Hanna
H
Almer
Sven
S
Askling
Johan
J
Ehlin
Anna
A
Ekbom
Anders
A
D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D016241:Child of Impaired Parents; D015209:Cholangitis, Sclerosing / Q000453:epidemiology*; D003093:Colitis, Ulcerative / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D013548:Sweden