Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium.
Genome-wide analyses of smoking behaviors in schizophrenia: Findings from the Psychiatric Genomics Consortium.
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DOI：
10.1016/j.jpsychires.2021.02.027
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发表时间：
2021-05
影响因子：
4.8
通讯作者：
Fanous AH
中科院分区：
文献类型：
--
作者：
Peterson RE;Bigdeli TB;Ripke S;Bacanu SA;Gejman PV;Levinson DF;Li QS;Rujescu D;Rietschel M;Weinberger DR;Straub RE;Walters JTR;Owen MJ;O'Donovan MC;Mowry BJ;Ophoff RA;Andreassen OA;Esko T;Petryshen TL;Kendler KS;Schizophrenia Working Group of the Psychiatric Genomics Consortium;Fanous AH
虽然17%的美国成年人经常吸烟，但精神分裂症患者的吸烟率超过60%。研究支持吸烟和精神分裂症的共同病因学基础，包括全基因组关联研究（GWAS）的发现。然而，很少有研究直接测试相同或不同的遗传变异是否也会影响精神分裂症患者的吸烟行为。使用精神病基因组学联盟（PGC）研究的精神分裂症（35476例，46839对照）的数据，我们估计这些性状之间的遗传相关性，并测试是否多基因风险评分（PRS）构建的吸烟行为GWAS的结果与精神分裂症的风险或吸烟行为的精神分裂症病例。结果表明，精神分裂症与开始吸烟（rg=0.159; P=5.05×10−10）、每天吸烟量（rg=0.094; P=0.006）和开始吸烟年龄（rg=0.10; P=0.009）之间存在显著的遗传相关性。精神分裂症患者与普通人群的吸烟行为比较，我们观察到吸烟开始（rg=0.624，P=0.002）和每日吸烟次数（rg=0.689，P=0.120）呈正遗传相关。同样，精神分裂症患者中，基于TAG的PRS的开始吸烟和每日吸烟次数与开始吸烟（P=3.49×10−5）和每日吸烟次数（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第一次GWAS，并在染色体7p21.3上的TMEM 106 B基因上游发现了一种新的与吸烟者每天吸烟的关联（rs 148253479，P=3.18×10−8，n=3520）。研究结果提供了精神分裂症和吸烟行为部分共享遗传基础的证据。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很大程度上是共享的。未来的研究应该解决这些关联的机制，以帮助精神分裂症和吸烟的治疗和预防工作。
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 (rg=0.159; P=5.05×10−10), cigarettes-smoked-per-day (rg=0.094; P=0.006), and age-of-onset of smoking (rg=0.10; P=0.009). Comparing smoking behaviors among schizophrenia cases to the general population, we observe positive genetic correlations for smoking initiation (rg=0.624, P=0.002) and cigarettes-smoked-per-day (rg=0.689, P=0.120). Similarly, TAG-based PRS for smoking initiation and cigarettes-smoked-per-day were significantly associated with smoking initiation (P=3.49×10−5) 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=3.18×10−8, 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.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
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影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
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Neale, Benjamin M.
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Brady, Owen A.;Zheng, Yanqiu;Hu, Fenghua
通讯作者：
Hu, Fenghua
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30.8
作者：
Bulik-Sullivan B;Finucane HK;Anttila V;Gusev A;Day FR;Loh PR;ReproGen Consortium;Psychiatric Genomics Consortium;Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3;Duncan L;Perry JR;Patterson N;Robinson EB;Daly MJ;Price AL;Neale BM
通讯作者：
Neale BM
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9.8
作者：
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通讯作者：
Zaitlen, Noah