Peterson Roseann E, Bigdeli Tim B, Ripke Stephan, Bacanu Silviu-Alin, Gejman Pablo V, Levinson Douglas F, Li Qingqin S, Rujescu Dan, Rietschel Marcella, Weinberger Daniel R, Straub Richard E, Walters James T R, Owen Michael J, O'Donovan Michael C, Mowry Bryan J, Ophoff Roel A, Andreassen Ole A, Esko Tõnu, Petryshen Tracey L, Kendler Kenneth S, Fanous Ayman H
Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
J Psychiatr Res. 2021 May;137:215-224. doi: 10.1016/j.jpsychires.2021.02.027. Epub 2021 Feb 18.
While 17% of US adults use tobacco regularly, smoking rates among persons with schizophrenia are upwards of 60%. Research supports a shared etiological basis for smoking and schizophrenia, including findings from genome-wide association studies (GWAS). However, few studies have directly tested whether the same or distinct genetic variants also influence smoking behavior among schizophrenia cases. Using data from the Psychiatric Genomics Consortium (PGC) study of schizophrenia (35476 cases, 46839 controls), we estimated genetic correlations between these traits and tested whether polygenic risk scores (PRS) constructed from the results of smoking behaviors GWAS were associated with schizophrenia risk or smoking behaviors among schizophrenia cases. Results indicated significant genetic correlations of schizophrenia with smoking initiation (r = 0.159; P = 5.05 × 10), cigarettes-smoked-per-day (r = 0.094; P = 0.006), and age-of-onset of smoking (r = 0.10; P = 0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (r = 0.624, P = 0.002) and cigarettes-smoked-per-day (r = 0.689, P = 0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P = 3.49 × 10) and cigarettes-smoked-per-day (P = 0.007) among schizophrenia cases. We performed the first GWAS of smoking behavior among schizophrenia cases and identified a novel association with cigarettes-smoked-per-day upstream of the TMEM106B gene on chromosome 7p21.3 (rs148253479, P = 3.18 × 10, n = 3520). Results provide evidence of a partially shared genetic basis for schizophrenia and smoking behaviors. Additionally, genetic risk factors for smoking behaviors were largely shared across schizophrenia and non-schizophrenia populations. Future research should address mechanisms underlying these associations to aid both schizophrenia and smoking treatment and prevention efforts.
虽然17%的美国成年人经常使用烟草，但精神分裂症患者的吸烟率高达60%以上。研究支持吸烟与精神分裂症存在共同的病因基础，包括全基因组关联研究（GWAS）的结果。然而，很少有研究直接测试相同或不同的基因变异是否也会影响精神分裂症患者的吸烟行为。利用精神基因组学联盟（PGC）精神分裂症研究的数据（35476例病例，46839例对照），我们估计了这些性状之间的遗传相关性，并测试了根据吸烟行为GWAS结果构建的多基因风险评分（PRS）是否与精神分裂症风险或精神分裂症患者的吸烟行为相关。结果表明，精神分裂症与吸烟起始（r = 0.159；P = 5.05×10）、每日吸烟量（r = 0.094；P = 0.006）和吸烟起始年龄（r = 0.10；P = 0.009）之间存在显著的遗传相关性。将精神分裂症患者的吸烟行为与普通人群进行比较，我们观察到吸烟起始（r = 0.624，P = 0.002）和每日吸烟量（r = 0.689，P = 0.120）存在正遗传相关性。同样，基于标签的吸烟起始和每日吸烟量的PRS与精神分裂症患者的吸烟起始（P = 3.49×10）和每日吸烟量（P = 0.007）显著相关。我们对精神分裂症患者的吸烟行为进行了首次GWAS，并在7号染色体p21.3上的TMEM106B基因上游发现了与每日吸烟量的新关联（rs148253479，P = 3.18×10，n = 3520）。结果为精神分裂症和吸烟行为提供了部分共同遗传基础的证据。此外，吸烟行为的遗传风险因素在精神分裂症和非精神分裂症人群中基本相同。未来的研究应探讨这些关联背后的机制，以帮助精神分裂症和吸烟的治疗及预防工作。
