Departmet of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, USA.
Sci Rep. 2020 Apr 24;10(1):6928. doi: 10.1038/s41598-020-63792-0.
Insomnia is one of the most prevalent and burdensome mental disorders worldwide, affecting between 10-20% of adults and up to 48% of the geriatric population. It is further associated with substance usage and dependence, as well other psychiatric disorders. In this study, we combined electronic health record (EHR) derived phenotypes and genotype information to conduct a genome wide analysis of insomnia in a 18,055 patient cohort. Diagnostic codes were used to identify 3,135 patients with insomnia. Our genome-wide association study (GWAS) identified one novel genomic risk locus on chromosome 8 (lead SNP rs17052966, p = 4.53 × 10, odds ratio = 1.28, se = 0.04). The heritability analysis indicated that common SNPs accounts for 7% (se = 0.02, p = 0.015) of phenotypic variation. We further conducted a large-scale meta-analysis of our results and summary statistics of two recent insomnia GWAS and 13 significant loci were identified. The genetic correlation analysis yielded a strong positive genetic correlation between insomnia and alcohol use (rG = 0.56, se = 0.14, p < 0.001), nicotine use (rG = 0.50, se = 0.12, p < 0.001) and opioid use (rG = 0.43, se = 0.18, p = 0.02) disorders, suggesting a significant common genetic risk factors between insomnia and substance use.
失眠是全球最普遍和负担最重的精神障碍之一，影响 10-20%的成年人，高达 48%的老年人群。它还与物质使用和依赖以及其他精神障碍有关。在这项研究中，我们结合电子健康记录（EHR）衍生的表型和基因型信息，对 18055 名患者队列进行了失眠的全基因组分析。使用诊断代码来确定 3135 名失眠患者。我们的全基因组关联研究（GWAS）在 8 号染色体上确定了一个新的基因组风险位点（先导 SNP rs17052966，p=4.53×10-8，优势比=1.28，se=0.04）。遗传分析表明，常见的 SNP 占表型变异的 7%（se=0.02，p=0.015）。我们进一步对我们的结果和两项最近的失眠 GWAS 的汇总统计数据进行了大规模荟萃分析，确定了 13 个显著位点。遗传相关性分析产生了失眠和酒精使用（rG=0.56，se=0.14，p<0.001）、尼古丁使用（rG=0.50，se=0.12，p<0.001）和阿片类物质使用（rG=0.43，se=0.18，p=0.02）障碍之间的强正遗传相关性，表明失眠和物质使用之间存在显著的共同遗传风险因素。
