Isomura K, Boman M, Rück C, Serlachius E, Larsson H, Lichtenstein P, Mataix-Cols D
Department of Clinical Neuroscience,Karolinska Institutet,Stockholm,Sweden.
Department of Medical Epidemiology and Biostatistics,Karolinska Institutet,Stockholm,Sweden.
Psychol Med. 2015 Jun;45(8):1581-9. doi: 10.1017/S0033291714002116. Epub 2014 Sep 12.
We aimed to provide unbiased estimates of familial risk and heritability of social anxiety disorder (SAD) and avoidant personality disorder (AVPD).
We identified 18 399 individuals diagnosed with SAD and 2673 with AVPD in the Swedish National Patient Register between 1997 and 2009. Risks (odds ratios; OR) for SAD in all biological and non-biological relatives of probands, compared to relatives of unaffected individuals were calculated. We also estimated the risks for AVPD in relatives of probands with SAD.
The risk for SAD among relatives of SAD probands increased proportionally to the degree of genetic relatedness. The risks for first-degree relatives [OR 4.74, 95% confidence interval (CI) 4.28-5.25] were significantly higher than for second-degree and third-degree relatives. Second-degree relatives (OR 2.30, 95% CI 2.01-2.63) had significantly higher risk than third-degree relatives (OR 1.72, 95% CI 1.52-1.94). Relatives at similar genetic distances had similar risks for SAD, despite different degrees of shared environment. Heritability was estimated to be approximately 56%. There were no significant sex differences in the familial patterns. The risk of AVPD in relatives of SAD probands was significantly elevated, even after excluding individuals with both diagnoses (first-degree OR 3.54, second-degree OR 2.20, third-degree OR 1.62). Non-biological relatives (spouses/partners) also had elevated risks for both SAD (OR 4.01) and AVPD (OR 3.85).
SAD clusters in families primarily due to genetic factors. SAD and AVPD are aetiologically related and may represent different expressions of the same vulnerability. The strong marital concordance observed in SAD/AVPD may indicate assortative mating but the exact mechanisms and implications require further investigation.
我们旨在对社交焦虑障碍(SAD)和回避型人格障碍(AVPD)的家族风险及遗传度进行无偏估计。
我们在瑞典国家患者登记处中识别出1997年至2009年间被诊断为SAD的18399人以及被诊断为AVPD的2673人。计算了先证者的所有生物学和非生物学亲属中SAD的风险(优势比;OR),并与未患病个体的亲属进行比较。我们还估计了SAD先证者亲属中AVPD的风险。
SAD先证者亲属中SAD的风险与遗传相关性程度成比例增加。一级亲属的风险[OR 4.74,95%置信区间(CI)4.28 - 5.25]显著高于二级和三级亲属。二级亲属(OR 2.30,95% CI 2.01 - 2.63)的风险显著高于三级亲属(OR 1.72,95% CI 1.52 - 1.94)。尽管共享环境程度不同,但遗传距离相似的亲属患SAD的风险相似。遗传度估计约为56%。家族模式中不存在显著的性别差异。即使排除同时患有两种诊断的个体,SAD先证者亲属中AVPD的风险仍显著升高(一级亲属OR 3.54,二级亲属OR 2.20,三级亲属OR 1.62)。非生物学亲属(配偶/伴侣)患SAD(OR 4.01)和AVPD(OR 3.85)的风险也升高。
SAD在家族中聚集主要是由于遗传因素。SAD和AVPD在病因上相关,可能代表相同易感性的不同表现形式。在SAD/AVPD中观察到的强烈婚姻一致性可能表明选型交配,但确切机制和影响需要进一步研究。