Using polygenic risk scores to investigate the evolution of smoking and mental health outcomes in UK biobank participants

IF 5.3 2区医学 Q1 PSYCHIATRY

Acta Psychiatrica Scandinavica Pub Date : 2023-08-21 DOI:10.1111/acps.13601

Lloyd Balbuena, Evyn Peters, Doug Speed

{"title":"Using polygenic risk scores to investigate the evolution of smoking and mental health outcomes in UK biobank participants","authors":"Lloyd Balbuena, Evyn Peters, Doug Speed","doi":"10.1111/acps.13601","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>Mendelian randomization studies report a bi-directional relation between cigarette smoking and mental disorders, yet from a clinical standpoint, mental disorders are the focus of treatment. Here, we used an event history framework to understand their evolution in the life course. Our objective was to estimate the relative contribution of genetic predispositions and self-reported smoking status (never, former, and present smoker) to hospitalizations for major depression, bipolar disorder, and schizophrenia.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We calculated polygenic risk scores (PRS) for ever smoking, pack-years of smoking as a proportion of adult life, and neuroticism in 337,140 UK Biobank participants of white British ancestry. These PRS and self-reported smoking status were entered as explanatory variables in survival models for hospitalization.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The estimated single nucleotide polymorphisms heritabilities (<i>h</i><sup>2</sup>) were 23%, 5.7%, and 5.7% for pack-years, ever smoking, and neuroticism respectively. PRS pack-years and PRS neuroticism were associated with higher hospitalization risk for mental disorders in all smoking status groups. The hazard for mental health hospitalization was higher in both previous (HR: 1.50, CI: 1.35–1.67) and current (HR: 3.58, 2.97–4.31) compared to never smokers, after adjusting for confounders.</p>\n </section>\n \n <section>\n \n <h3> Conclusion</h3>\n \n <p>Since genetic liabilities for smoking and neuroticism are fixed at conception and smoking initiation generally started before age 20, our results show that preventing smoking in adolescents probably prevents the development of mental disorders.</p>\n </section>\n </div>","PeriodicalId":108,"journal":{"name":"Acta Psychiatrica Scandinavica","volume":"148 5","pages":"447-456"},"PeriodicalIF":5.3000,"publicationDate":"2023-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acps.13601","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Psychiatrica Scandinavica","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/acps.13601","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 1

Abstract

Objective

Mendelian randomization studies report a bi-directional relation between cigarette smoking and mental disorders, yet from a clinical standpoint, mental disorders are the focus of treatment. Here, we used an event history framework to understand their evolution in the life course. Our objective was to estimate the relative contribution of genetic predispositions and self-reported smoking status (never, former, and present smoker) to hospitalizations for major depression, bipolar disorder, and schizophrenia.

Methods

We calculated polygenic risk scores (PRS) for ever smoking, pack-years of smoking as a proportion of adult life, and neuroticism in 337,140 UK Biobank participants of white British ancestry. These PRS and self-reported smoking status were entered as explanatory variables in survival models for hospitalization.

Results

The estimated single nucleotide polymorphisms heritabilities (h²) were 23%, 5.7%, and 5.7% for pack-years, ever smoking, and neuroticism respectively. PRS pack-years and PRS neuroticism were associated with higher hospitalization risk for mental disorders in all smoking status groups. The hazard for mental health hospitalization was higher in both previous (HR: 1.50, CI: 1.35–1.67) and current (HR: 3.58, 2.97–4.31) compared to never smokers, after adjusting for confounders.

Conclusion

Since genetic liabilities for smoking and neuroticism are fixed at conception and smoking initiation generally started before age 20, our results show that preventing smoking in adolescents probably prevents the development of mental disorders.

Abstract Image

查看原文本刊更多论文

使用多基因风险评分调查英国生物库参与者吸烟和心理健康结果的演变。

目的：孟德尔随机化研究报告了吸烟与精神障碍之间的双向关系，但从临床角度来看，精神障碍是治疗的重点。在这里，我们使用了一个事件历史框架来了解它们在生命过程中的演变。我们的目的是评估遗传易感性和自我报告的吸烟状况（从未吸烟、以前吸烟和现在吸烟）对严重抑郁症、双相情感障碍和精神分裂症住院的相对贡献。方法：我们计算了337140名具有英国白人血统的英国生物银行参与者的吸烟多基因风险评分（PRS）、吸烟年限占成年生活的比例以及神经质。这些PRS和自我报告的吸烟状况被输入作为住院生存模型的解释变量。结果：估计的单核苷酸多态性遗传性（h2）对于包龄、吸烟和神经质分别为23%、5.7%和5.7%。在所有吸烟状态组中，PRS包年和PRS神经质与较高的精神障碍住院风险相关。校正混杂因素后，与从不吸烟者相比，既往（HR:1.50，CI:1.35-1.67）和当前（HR:3.58,2.97-4.31）精神健康住院的风险更高。结论：由于吸烟和神经质的遗传责任在受孕时是固定的，吸烟通常在20岁之前开始，我们的研究结果表明，预防青少年吸烟可能会预防精神障碍的发展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Psychiatrica Scandinavica 医学-精神病学

CiteScore

11.20

自引率

3.00%

发文量

135

审稿时长

6-12 weeks

期刊介绍： Acta Psychiatrica Scandinavica acts as an international forum for the dissemination of information advancing the science and practice of psychiatry. In particular we focus on communicating frontline research to clinical psychiatrists and psychiatric researchers. Acta Psychiatrica Scandinavica has traditionally been and remains a journal focusing predominantly on clinical psychiatry, but translational psychiatry is a topic of growing importance to our readers. Therefore, the journal welcomes submission of manuscripts based on both clinical- and more translational (e.g. preclinical and epidemiological) research. When preparing manuscripts based on translational studies for submission to Acta Psychiatrica Scandinavica, the authors should place emphasis on the clinical significance of the research question and the findings. Manuscripts based solely on preclinical research (e.g. animal models) are normally not considered for publication in the Journal.