A Developmentally-Informative Genome-wide Association Study of Alcohol Use Frequency

IF 2.6 4区医学 Q2 BEHAVIORAL SCIENCES Behavior Genetics Pub Date : 2023-12-18 DOI:10.1007/s10519-023-10170-x

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Abstract

Contemporary genome-wide association study (GWAS) methods typically do not account for variability in genetic effects throughout development. We applied genomic structural equation modeling to combine developmentally-informative phenotype data and GWAS to create polygenic scores (PGS) for alcohol use frequency that are specific to developmental stage. Longitudinal cohort studies targeted for gene-identification analyses include the Collaborative Study on the Genetics of Alcoholism (adolescence n = 1,118, early adulthood n = 2,762, adulthood n = 5,255), the National Longitudinal Study of Adolescent to Adult Health (adolescence n = 3,089, early adulthood n = 3,993, adulthood n = 5,149), and the Avon Longitudinal Study of Parents and Children (ALSPAC; adolescence n = 5,382, early adulthood n = 3,613). PGS validation analyses were conducted in the COGA sample using an alternate version of the discovery analysis with COGA removed. Results suggest that genetic liability for alcohol use frequency in adolescence may be distinct from genetic liability for alcohol use frequency later in developmental periods. The age-specific PGS predicts an increase of 4 drinking days per year per PGS standard deviation when modeled separately from the common factor PGS in adulthood. The current work was underpowered at all steps of the analysis plan. Though small sample sizes and low statistical power limit the substantive conclusions that can be drawn regarding these research questions, this work provides a foundation for future genetic studies of developmental variability in the genetic underpinnings of alcohol use behaviors and genetically-informed, age-matched phenotype prediction.

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一项关于酒精使用频率的全基因组发育信息关联研究

摘要当代的全基因组关联研究（GWAS）方法通常不考虑整个发育过程中遗传效应的变异性。我们应用基因组结构方程建模法，将发育信息表型数据和全基因组关联研究结合起来，为酒精使用频率创建了特定于发育阶段的多基因评分（PGS）。基因鉴定分析所针对的纵向队列研究包括酗酒遗传学合作研究（青春期 n = 1,118 人，成年早期 n = 2,762 人，成年期 n = 5,255 人）、全国青少年到成人健康纵向研究（青春期 n = 3,089 人，成年早期 n = 3,993 人，成年期 n = 5,149 人）和雅芳父母与子女纵向研究（ALSPAC；青春期 n = 5,382 人，成年早期 n = 3,613 人）。在 COGA 样本中进行了 PGS 验证分析，使用的是去掉 COGA 的另一个发现分析版本。结果表明，青春期酗酒频率的遗传责任可能有别于发育后期酗酒频率的遗传责任。如果将特定年龄的 PGS 与成年期的共同因素 PGS 分开建模，则预测每一个 PGS 标准差每年会增加 4 个饮酒日。目前的研究工作在分析计划的所有步骤中都存在动力不足的问题。虽然样本量小、统计能力低，限制了对这些研究问题得出实质性结论，但这项工作为未来对酒精使用行为遗传基础的发育变异性进行遗传研究以及根据遗传信息进行年龄匹配表型预测奠定了基础。

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来源期刊

Behavior Genetics 生物-行为科学

CiteScore

4.90

自引率

7.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Behavior Genetics - the leading journal concerned with the genetic analysis of complex traits - is published in cooperation with the Behavior Genetics Association. This timely journal disseminates the most current original research on the inheritance and evolution of behavioral characteristics in man and other species. Contributions from eminent international researchers focus on both the application of various genetic perspectives to the study of behavioral characteristics and the influence of behavioral differences on the genetic structure of populations.