Leveraging Genomic Data to Examine the Causal Impact of Alcohol, Tobacco, Cannabis, and Opioid Use on Biological and Cognitive Ageing

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jared V. Balbona, Paul Jeffries, Aaron J. Gorelik, Elliot C. Nelson, Ryan Bogdan, Arpana Agrawal, Emma C. Johnson
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Abstract

Although substance use is associated with a shortened lifespan, impeded health and accelerated biological ageing, the factors contributing to the associations between substance use and ageing are poorly understood. We used summary statistics from genome-wide association studies (GWAS) to investigate whether substance involvement (N from 28K to 2M)—including alcohol, tobacco, cannabis and opioid use and use disorders—is genetically correlated with various ageing metrics (N from 162K to 2.7M) and whether these correlations reflect shared genetic etiologies or putative causal relationships. Using Linkage Disequilibrium Score Regression (LDSC), we found widespread evidence of genetic correlations between substance use/use disorders and indices of physical, cognitive and biological ageing. We then employed a series of Mendelian randomization–based approaches, finding significant causal effects of genetic predispositions to both tobacco use disorder and quantity of tobacco smoked on various markers of ageing. Causal effects of problematic alcohol use and cannabis use disorder were also found, though findings were mixed. Evidence of reverse causality (i.e., ageing causing substance use), meanwhile, was scant. Collectively, these results demonstrate strong triangulation across approaches and highlight the importance of integrating genetic insights into public health strategies for reducing the burden of SUDs across the lifespan.

Abstract Image

利用基因组数据研究酒精、烟草、大麻和阿片类药物使用对生物和认知衰老的因果影响
尽管药物使用与寿命缩短、健康受损和加速生物衰老有关,但人们对导致药物使用与衰老之间关联的因素了解甚少。我们使用全基因组关联研究(GWAS)的汇总统计数据来调查物质参与(N从28K到2M)——包括酒精、烟草、大麻和阿片类药物的使用和使用障碍——是否与各种衰老指标(N从162K到2.7M)存在遗传相关性,以及这些相关性是否反映了共同的遗传病因或假定的因果关系。使用连锁不平衡评分回归(LDSC),我们发现物质使用/使用障碍与身体、认知和生物衰老指标之间存在广泛的遗传相关性。然后,我们采用了一系列基于孟德尔随机化的方法,发现遗传倾向对烟草使用障碍和吸烟数量对各种衰老标志物的显著因果影响。问题酒精使用和大麻使用障碍的因果影响也被发现,尽管结果好坏参半。与此同时,反向因果关系(即衰老导致药物使用)的证据很少。总的来说,这些结果显示了跨方法的强大三角测量,并强调了将遗传见解纳入公共卫生战略以减轻整个生命周期中sud负担的重要性。
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来源期刊
Addiction Biology
Addiction Biology 生物-生化与分子生物学
CiteScore
8.10
自引率
2.90%
发文量
118
审稿时长
6-12 weeks
期刊介绍: Addiction Biology is focused on neuroscience contributions and it aims to advance our understanding of the action of drugs of abuse and addictive processes. Papers are accepted in both animal experimentation or clinical research. The content is geared towards behavioral, molecular, genetic, biochemical, neuro-biological and pharmacology aspects of these fields. Addiction Biology includes peer-reviewed original research reports and reviews. Addiction Biology is published on behalf of the Society for the Study of Addiction to Alcohol and other Drugs (SSA). Members of the Society for the Study of Addiction receive the Journal as part of their annual membership subscription.
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