Hereditary factors in primary biliary cholangitis (PBC) have been well defined in genome‐wide association studies, but there are few direct data available that define the relative risk (RR) 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 this study was to use the unique Icelandic genealogical database to study the familiality of PBC. All patients with positive antimitochondrial antibody measurements in Iceland during the period 1991‐2015 who fulfilled 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, sex, and number of known relatives were randomly chosen from this database to calculate the familial RR of PBC. The average kinship coefficient (KC) of the patients was calculated and compared with the average KC of controls. Overall, 222 PBC patients were identified (182 females, 40 males; median age, 62 years). First‐, second‐ and third‐degree relatives of the PBC patients had a high RR 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 RR was also increased to 1.66 (P = 0.08) and 1.42 (P = 0.08), respectively. The average KC of the patients was also higher than that of the control subjects, with 21.34 × 10−5 versus 9.56 × 10−5 (P < 0.0001). 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. (Hepatology 2018;68:166‐171).

中文翻译：

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使用冰岛家谱数据库定义原发性胆汁性胆管炎的家族风险

原发性胆汁性胆管炎 (PBC) 的遗传因素已在全基因组关联研究中得到很好的定义，但很少有直接数据可用于定义受累先证者家庭成员的相对风险 (RR)。多项研究已经证明一级亲属的风险增加，但缺乏关于后代更详细关联的数据。本研究的目的是使用独特的冰岛家谱数据库来研究 PBC 的家族性。1991 年至 2015 年期间冰岛所有抗线粒体抗体检测阳性且符合 PBC 诊断标准的患者均被纳入研究。冰岛家谱数据库用于评估家庭关系。对于每个 PBC 病例，10,000 名对照受试者的年龄、性别、从该数据库中随机选择已知亲属的数量来计算 PBC 的家族性 RR。计算患者的平均亲属系数 (KC) 并与对照组的平均 KC 进行比较。总共确定了 222 名 PBC 患者（182 名女性，40 名男性；中位年龄，62 岁）。PBC 患者的一级、二级和三级亲属具有较高的疾病 RR：分别为 9.13（P < 0.0001）、3.61（P = 0.014）和 2.59（P = 0.008）。在四级和五级亲属中，RR 也分别增加到 1.66 (P = 0.08) 和 1.42 (P = 0.08)。患者的平均 KC 也高于对照组，分别为 21.34 × 10-5 和 9.56 × 10-5（P < 0.0001）。结论：与对照组相比，PBC 患者的亲属患该病的风险明显更高，重要的是，我们的数据表明，即使在二级和三级亲属中，风险也显着增加。（肝病学 2018 年；68：166-171）。