Costello E Jane, Eaves Lindon, Sullivan Patrick, Kennedy Martin, Conway Kevin, Adkins Daniel E, Angold A, Clark Shaunna L, Erkanli Alaattin, McClay Joseph L, Copeland William, Maes Hermine H, Liu Youfang, Patkar Ashwin A, Silberg Judy, van den Oord Edwin
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA.
Twin Res Hum Genet. 2013 Apr;16(2):505-15. doi: 10.1017/thg.2013.6. Epub 2013 Mar 6.
The importance of including developmental and environmental measures in genetic studies of human pathology is widely acknowledged, but few empirical studies have been published. Barriers include the need for longitudinal studies that cover relevant developmental stages and for samples large enough to deal with the challenge of testing gene-environment-development interaction. A solution to some of these problems is to bring together existing data sets that have the necessary characteristics. As part of the National Institute on Drug Abuse-funded Gene-Environment-Development Initiative, our goal is to identify exactly which genes, which environments, and which developmental transitions together predict the development of drug use and misuse. Four data sets were used of which common characteristics include (1) general population samples, including males and females; (2) repeated measures across adolescence and young adulthood; (3) assessment of nicotine, alcohol, and cannabis use and addiction; (4) measures of family and environmental risk; and (5) consent for genotyping DNA from blood or saliva. After quality controls, 2,962 individuals provided over 15,000 total observations. In the first gene-environment analyses, of alcohol misuse and stressful life events, some significant gene-environment and gene-development effects were identified. We conclude that in some circumstances, already collected data sets can be combined for gene-environment and gene-development analyses. This greatly reduces the cost and time needed for this type of research. However, care must be taken to ensure careful matching across studies and variables.
在人类病理学的基因研究中纳入发育和环境测量的重要性已得到广泛认可,但已发表的实证研究却很少。障碍包括需要进行涵盖相关发育阶段的纵向研究,以及需要足够大的样本量来应对测试基因-环境-发育相互作用的挑战。解决其中一些问题的方法是汇集具有必要特征的现有数据集。作为美国国立药物滥用研究所资助的基因-环境-发育倡议的一部分,我们的目标是准确确定哪些基因、哪些环境以及哪些发育转变共同预测药物使用和滥用的发展。我们使用了四个数据集,其共同特征包括:(1)一般人群样本,包括男性和女性;(2)在青春期和青年期的重复测量;(3)对尼古丁、酒精和大麻使用及成瘾的评估;(4)家庭和环境风险测量;(5)同意对血液或唾液中的DNA进行基因分型。经过质量控制后,2962名个体提供了超过15000条总观测数据。在首次基因-环境分析中,对酒精滥用和应激性生活事件进行分析时,发现了一些显著的基因-环境和基因-发育效应。我们得出结论,在某些情况下,可以将已收集的数据集合并用于基因-环境和基因-发育分析。这大大降低了这类研究所需的成本和时间。然而,必须谨慎确保各研究和变量之间的仔细匹配。