Familial aggregation of atrial fibrillation in Iceland
Familial aggregation of atrial fibrillation in Iceland
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DOI：
10.1093/eurheartj/ehi727
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发表时间：
2006-03-01
影响因子：
39.3
通讯作者：
Stefansson, K
中科院分区：
文献类型：
--
作者：
Arnar, DO;Thorvaldsson, S;Stefansson, K
目的研究冰岛人心房颤动（AF）的遗传性，利用全国范围的家谱数据库和基于人群的AF数据。AF是一种患病率高的疾病，已知在家庭中聚集，方法和结果研究人群包括自1987年以来确诊的5269例患者，年龄-性别-从家谱数据库中随机选择的匹配对照。亲属系数（KC），表示为系谱指数的家庭（GIF=平均KC × 100 000），计算之前和之后的亲属分离的1至5个减数分裂事件。计算一至五级亲属的风险比（RR）。房颤患者的平均成对GIF为15.9（对照组的平均GIF为13.9，95%CI=13.3，14.4）;下降到15.4（对照组平均GIF为13.6，95%CI=13.1，14.2），排除一次减数分裂分离的亲属后为13.7（对照组的平均GIF为12.6，95%CI=12.1，13.2），12.7（对照组的平均GIF为11.9，95%CI=11.4，12.4）和11.3（对照组平均GIF为10.6，95%CI=10.1，11.1），排除2、3、4次减数分裂内的亲属后（均P < 0.00001）。亲属对之间的RR也逐渐下降，从一级亲属的1.77下降到二级到五级亲属的1.36、1.18、1.10和1.05（均P < 0.001），这与血统相同的等位基因比例下降一致。当分析仅限于60岁之前诊断为AF的受试者时，AF病例的一级亲属患AF的可能性是一般人群的近5倍，AF比一般人群高出近5倍。结论AF在冰岛的Cirrhosis患者中显示出强有力的遗传性证据，这表明可能存在未发现的遗传变异的风险，AF的常见形式。
Aims To examine the heritability of atrial fibrillation (AF) in Icelanders, utilizing a nationwide genealogy database and population-based data on AF. AF is a disorder with a high prevalence, which has been known to cluster in families, but the heritability of the common form has not been well defined.Methods and results The study population included 5269 patients diagnosed since 1987 and age-sex-matched controls randomly selected from the genealogy database. Kinship coefficients (KC), expressed as genealogical index of familiality (GIF=average KCx100 000), were calculated before and after exclusion of relatives separated by one to five meiotic events. Risk ratios (RR) were calculated for first- to fifth-degree relatives. The average pairwise GIF among patients with AF was 15.9 (mean GIF for controls 13.9, 95%CI=13.3, 14.4); this declined to 15.4 (mean GIF for controls 13.6, 95%CI=13.1, 14.2) after exclusion of relatives separated by one meiosis and to 13.7 (mean GIF for controls 12.6, 95%CI=12.1, 13.2), 12.7 (mean GIF for controls 11.9, 95%CI=11.4, 12.4), and 11.3 (mean GIF for controls 10.6, 95%CI=10.1, 11.1) after exclusion of relatives within two, three, and four meioses, respectively (all P < 0.00001). RRs among relative pairs also declined incrementally, from 1.77 in first-degree relatives to 1.36, 1.18, 1.10, and 1.05 in second- through fifth-degree relatives (all P < 0.001), consistent with the declining proportion of alleles shared identically by descent. When the analysis was limited to subjects diagnosed with AF before the age of 60, first-degree relatives of the AF cases were nearly five times more likely to have AF than the general population.Conclusion AF shows strong evidence of heritability among unselected patients in Iceland, suggesting that there may be undiscovered genetic variants underlying the risk of the common form of AF.