To investigate the genetic contribution to amyotrophic lateral sclerosis (ALS) and the phenotypic and genetic associations between ALS and psychiatric and cardiovascular disorders (CVD) we used the national registry data from Denmark linked to first-degree relatives to estimate heritability and cross-trait parameters.

ALS cases and 100 sex and birth-matched controls per case from the Danish Civil Registration System were linked to their records in the Danish National Patient Registry. Cases and controls were compared for (1) risk of ALS in first-degree relatives, used to estimate heritability, (2) comorbidity with psychiatric disorders and CVD, and (3) risk of psychiatric disorders and CVD in first-degree relatives.

5,808 ALS cases and 580,800 controls were identified. Fifteen percent of cases and controls could be linked to both parents and full siblings, whereas 70% could be linked to children. (1) We estimated the heritability of ALS to be 0.43 (95% CI, 0.34–0.53). (2) We found increased rates of diagnosis of mental disorders (risk ratio = 1.18; 95% CI, 1.09–1.29) and CVD in those later diagnosed with ALS. (3) In first-degree relatives of those with ALS, we found increased rate of schizophrenia (1.17; 95% CI, 0.96–1.42), but no evidence for increased risk CVD.

Heritability of ALS is lower than commonly reported. There is likely a genetic relationship between ALS and schizophrenia, and a nongenetic relationship between ALS and CVD.

为了研究对肌萎缩侧索硬化症 (ALS) 的遗传贡献以及 ALS 与精神和心血管疾病 (CVD) 之间的表型和遗传关联，我们使用来自丹麦的与一级亲属相关的国家登记数据来估计遗传力和交叉性状参数.

来自丹麦民事登记系统的 ALS 病例和每个病例的 100 个性别和出生匹配对照与他们在丹麦国家患者登记处的记录相关联。比较病例和对照的（1）一级亲属患 ALS 的风险，用于估计遗传力，（2）精神疾病和 CVD 的共病，以及（3）一级亲属的精神疾病和 CVD 风险。

确定了 5,808 例 ALS 病例和 580,800 例对照。15% 的病例和对照可能与父母和全兄弟姐妹有关，而 70% 可能与儿童有关。(1) 我们估计 ALS 的遗传力为 0.43 (95% CI, 0.34–0.53)。(2) 我们发现后来被诊断为 ALS 的患者的精神障碍（风险比 = 1.18；95% CI，1.09-1.29）和 CVD 的诊断率增加。(3) 在 ALS 患者的一级亲属中，我们发现精神分裂症的发病率增加（1.17；95% CI，0.96-1.42），但没有证据表明 CVD 风险增加。

ALS 的遗传力低于通常报道的。ALS 和精神分裂症之间可能存在遗传关系，而 ALS 和 CVD 之间可能存在非遗传关系。