蛋白质与酒精消费和酒精相关社会医学状况遗传风险的关系

IF 2.6 3区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Gabin Drouard, Teemu Palviainen, Chia-Ling Kuo, Breno S. Diniz, Xiaoling Wang, Miina Ollikainen, Antti Latvala, Jaakko Kaprio
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引用次数: 0

摘要

研究蛋白质组学与饮酒的关联以及这些蛋白质与酒精相关性状的遗传联系的研究很少。我们研究的目的是:(1)确定与饮酒相关的蛋白质;(2)研究将已确定的蛋白质与饮酒和相关社会医学状况联系起来的分子途径和遗传学。我们从387名芬兰双胞胎(年龄范围:56-70岁)的血液样本中生成了蛋白质组学和基因型数据,并计算了八种酒精相关特征的多基因风险评分(PRSs):肥胖、酒精依赖、每周饮酒次数、每天吸烟次数、重度抑郁症(mdd)、精神分裂症、外化行为和受教育程度。在Bonferroni校正和BMI、性别和年龄调整后,我们从2321种蛋白质中鉴定出20种与饮酒相关的蛋白质,以每月乙醇克数表示。对同卵双胞胎进行的对内分析表明,在考虑了遗传混杂因素后,一些已确定的关联仍然存在。虽然只有代表每周饮酒数量遗传风险的PRS与饮酒有关,但有几种蛋白质与PRS有关,特别是MDD的PRS。所有鉴定出的蛋白质在英国生物银行中都得到了显著的复制,途径分析表明,它们与饮酒的集体联系可以用氧化应激和细胞损伤来解释。总之,我们确定了几种与酒精相关的血浆蛋白,它们的水平也与精神疾病和药物使用的遗传风险有关。我们的研究表明,蛋白质作为早期检测酒精相关疾病的生物标志物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Protein Associations With Alcohol Consumption and Genetic Risk for Alcohol-Related Sociomedical Conditions

Protein Associations With Alcohol Consumption and Genetic Risk for Alcohol-Related Sociomedical Conditions

Studies investigating proteomic associations with alcohol consumption and the genetic links of these proteins to alcohol-related traits are scarce. The aims of our study were (1) to identify proteins associated with alcohol consumption and (2) to investigate the molecular pathways and genetics linking the identified proteins to alcohol consumption and related sociomedical conditions. We generated proteomic and genotypic data from blood samples of 387 Finnish twins (age range: 56–70) and calculated polygenic risk scores (PRSs) of eight alcohol-related traits: obesity, alcohol dependence, number of drinks per week, number of cigarettes per day, major depressive disorders (MDDs), schizophrenia, externalising behaviour and educational attainment. We identified 20 (out of 2321) proteins associated with alcohol consumption, expressed as log ethanol grams per month, after Bonferroni correction and adjustment for BMI, sex and age. Within-pair analyses in monozygotic twin pairs showed that some of the identified associations persisted after accounting for genetic confounding. While only the PRS representing genetic risk for the number of alcoholic drinks per week was associated with alcohol consumption, several proteins were associated with PRSs, in particular the PRS of MDD. All identified proteins were significantly replicated in the UK Biobank, and pathway analysis suggested their collective connection to alcohol consumption might be explained by oxidative stress and cell damage. In conclusion, we identified several alcohol-associated plasma proteins whose levels are also linked to genetic risk for mental illness and substance use. Our study suggests the potential of proteins as biomarkers for early detection of alcohol-related disorders.

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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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