Using the Icelandic Genealogical Database to define the familial risk of primary biliary cholangitis

Abstract

Hereditary factors in primary biliary cholangitis (PBC) have been well defined in genome wide-association studies but there is not much direct data available that define the relative risk for family members with an affected proband. An increased risk in first-degree relatives has been demonstrated in a variety of studies but data have been lacking on further detailed associations for subsequent generations. The objective of the study was to use the unique Icelandic genealogical database to study the familiality of PBC. All patients with positive anti-mitochondrial antibodies measurements in Iceland during the period of 1991-2015, fulfilling diagnostic criteria for PBC were included. The Icelandic Genealogical Database was used to assess familial relations. For each case of PBC, 10,000 control subjects matched for age, gender and number of known relatives were randomly chosen from this database to calculate the familial relative risk of PBC. The average kinship coefficient (KC) of the patients was calculated and compared to the average kinship coefficient of controls. Overall 222 PBC patients were identified, 182 females and 40 males, median age 62 years. First-, second- and third-degree relatives of the PBC patients had a high relative risk of the disease: 9.13 (p<0.0001), 3.61 (p=0.014) and 2.59 (p=0.008), respectively. In fourth- and fifth-degree relatives the relative risk was also increased, with 1.66 (p=0.08) and 1.42 (p=0.08), respectively. The average kinship coefficient of the patients was also higher than that of the control subjects, with 21.34 x10-5 vs. 9.56 x10-5 (p<0.0001). In conclusion relatives of PBC patients had markedly higher risk for development of the disease compared with controls and importantly our data demonstrate that the risk was significantly increased even in second- and third-degree relatives. This article is protected by copyright. All rights reserved.

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