Archer Natalie P, Wilkinson Anna V, Ranjit Nalini, Wang Jian, Zhao Hua, Swann Alan C, Shete Sanjay
Environmental Epidemiology and Disease Registries Section, Texas Department of State Health Services Austin, Texas.
Austin Regional Campus, University of Texas School of Public Health Austin, Texas.
Brain Behav. 2014 Jul;4(4):521-30. doi: 10.1002/brb3.236. Epub 2014 May 16.
The genetic heritability for sensation-seeking tendencies ranges from 40 to 60%. Sensation-seeking behaviors typically manifest during adolescence and are associated with alcohol and cigarette experimentation in adolescents. Social disinhibition is an aspect of sensation-seeking that is closely tied to cigarette and alcohol experimentation.
We examined the contribution of candidate genes to social disinhibition among 1132 Mexican origin youth in Houston, Texas, adjusting for established demographic and psychosocial risk factors. Saliva samples were obtained at baseline in 2005-06, and social disinhibition and other psychosocial data were obtained in 2008-09. Participants were genotyped for 672 functional and tagging SNPs potentially related to sensation-seeking, risk-taking, smoking, and alcohol use.
Six SNPs were significantly associated with social disinhibition scores, after controlling for false discovery and adjusting for population stratification and relevant demographic/psychosocial characteristics. Minor alleles for three of the SNPs (rs1998220 on OPRM1; rs9534511 on HTR2A; and rs4938056 on HTR3B) were associated with increased risk of social disinhibition, while minor alleles for the other three SNPs (rs1003921 on KCNC1; rs16116 downstream of NPY; and rs16870286 on LINC00518) exhibited a protective effect. Age, linguistic acculturation, thrill and adventure-seeking, and drug and alcohol-seeking were all significantly positively associated with increased risk of social disinhibition in a multivariable model (P < 0.001).
These results add to our knowledge of genetic risk factors for social disinhibition. Additional research is needed to verify whether these SNPs are associated with social disinhibition among youth of different ethnicities and nationalities, and to elucidate whether and how these SNPs functionally contribute to social disinhibition.
寻求刺激倾向的遗传度在40%至60%之间。寻求刺激行为通常在青春期出现,并与青少年的酒精和香烟尝试行为相关。社会抑制是寻求刺激的一个方面,与香烟和酒精尝试密切相关。
我们研究了候选基因对德克萨斯州休斯顿1132名墨西哥裔青少年社会抑制的影响,并对既定的人口统计学和心理社会风险因素进行了调整。2005 - 2006年在基线时采集唾液样本,2008 - 2009年获取社会抑制及其他心理社会数据。对参与者进行了672个可能与寻求刺激、冒险、吸烟和饮酒相关的功能性和标签单核苷酸多态性(SNP)基因分型。
在控制错误发现率并对人群分层及相关人口统计学/心理社会特征进行调整后,有六个SNP与社会抑制得分显著相关。其中三个SNP(OPRM1上的rs1998220;HTR2A上的rs9534511;HTR3B上的rs4938056)的次要等位基因与社会抑制风险增加相关,而另外三个SNP(KCNC1上的rs1003921;NPY下游的rs16116;LINC00518上的rs16870286)的次要等位基因则具有保护作用。在多变量模型中,年龄、语言文化适应、寻求刺激和冒险以及寻求毒品和酒精均与社会抑制风险增加显著正相关(P < 0.001)。
这些结果增加了我们对社会抑制遗传风险因素的认识。需要进一步研究以验证这些SNP是否与不同种族和民族青少年的社会抑制相关,并阐明这些SNP是否以及如何在功能上导致社会抑制。