Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.
Genetic correlation between amyotrophic lateral sclerosis and schizophrenia.
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DOI：
10.1038/ncomms14774
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发表时间：
2017-03-21
影响因子：
16.6
通讯作者：
Schizophrenia Working Group of the Psychiatric Genomics Consortium
中科院分区：
文献类型：
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作者：
McLaughlin RL;Schijven D;van Rheenen W;van Eijk KR;O'Brien M;Kahn RS;Ophoff RA;Goris A;Bradley DG;Al-Chalabi A;van den Berg LH;Luykx JJ;Hardiman O;Veldink JH;Project MinE GWAS Consortium;Schizophrenia Working Group of the Psychiatric Genomics Consortium
我们之前的研究表明，肌萎缩侧索硬化症（ALS）患者的亲属患精神分裂症的比率高于预期，这表明两种疾病之间存在病因学关系。在这里，我们使用来自超过100,000个独特个体的全基因组关联研究数据来研究ALS和精神分裂症之间的遗传关系。使用连锁不平衡评分回归，我们估计ALS和精神分裂症之间的遗传相关性为14.3% (7.05-21.6；P=1 × 10−4)，精神分裂症多基因风险评分解释了ALS方差的0.12% （P=8.4 × 10−7）。鉴于这些发现（优势比1.08-1.26），预计ALS和精神分裂症的合并症会适度增加，但这需要非常大规模的研究来进行流行病学观察。我们使用条件错误发现率分析确定了五个潜在的新的als相关基因座。这两种疾病之间共享的神经生物学机制可能会在未来的临床前和临床研究中产生新的假设。肌萎缩性侧索硬化症患者的亲属有意想不到的高发病率的精神分裂症。在这里，作者展示了这两种情况之间的遗传联系，表明了共同的神经生物学机制。
We have previously shown higher-than-expected rates of schizophrenia in relatives of patients with amyotrophic lateral sclerosis (ALS), suggesting an aetiological relationship between the diseases. Here, we investigate the genetic relationship between ALS and schizophrenia using genome-wide association study data from over 100,000 unique individuals. Using linkage disequilibrium score regression, we estimate the genetic correlation between ALS and schizophrenia to be 14.3% (7.05–21.6; P=1 × 10−4) with schizophrenia polygenic risk scores explaining up to 0.12% of the variance in ALS (P=8.4 × 10−7). A modest increase in comorbidity of ALS and schizophrenia is expected given these findings (odds ratio 1.08–1.26) but this would require very large studies to observe epidemiologically. We identify five potential novel ALS-associated loci using conditional false discovery rate analysis. It is likely that shared neurobiological mechanisms between these two disorders will engender novel hypotheses in future preclinical and clinical studies. Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.