Hong Jinkuk, DaWalt Leann, Baker Mei Wang, Berry-Kravis Elizabeth M, Mailick Marsha R
Waisman Center, University of Wisconsin-Madison, Madison, WI, United States.
Wisconsin State Laboratory of Hygiene, Madison, WI, United States.
Front Psychiatry. 2021 Aug 11;12:727085. doi: 10.3389/fpsyt.2021.727085. eCollection 2021.
CGG repeat length was assayed in 5499 research participants (2637 men and 2862 women) in the Wisconsin Longitudinal Study (WLS), a population-based cohort. Most past research has focused on clinically-ascertained individuals with expansions in CGG repeats, either those with fragile X syndrome (> 200 CGG repeats), the premutation (55-200 repeats), or in the gray zone (variously defined as 45-54 or 41-54 repeats). In contrast, the WLS is a unique source of data that was obtained from an unselected cohort of individuals from the general population for whom CGG repeat length was assayed. The WLS is a random sample of one-third of all high school seniors in the state of Wisconsin in 1957. The most recent round of data collection was in 2011; thus, the study spanned over 50 years. Saliva samples were obtained from 69% of surviving members of the cohort in 2008 and 2011, from which CGG repeats were assayed. With one exception, the CGG repeat length of all members of this cohort was below 100 (ranging from 7 to 84). The present study evaluated the genotype-phenotype associations of CGG repeat number and IQ, college graduation, age at menopause, number of biological children, having a child with intellectual or developmental disabilities, and the likelihood of experiencing an episode of depression during adulthood. Linear and curvilinear effects were probed. Although effect sizes were small, significant associations were found between CGG repeat length and high school IQ score, college graduation, number of biological children, age at menopause, and the likelihood of having an episode of depression. However, there was no significant association between repeat length and having a child diagnosed with an IDD condition. This study demonstrates a continuum of phenotype effects with repeat lengths and illustrates how research inspired by a rare genetic condition (such as fragile X syndrome) can be used to probe genotype-phenotype associations in the general population.
在以人群为基础的队列研究——威斯康星纵向研究（WLS）中，对5499名研究参与者（2637名男性和2862名女性）的CGG重复序列长度进行了检测。过去的大多数研究都集中在临床确诊的CGG重复序列扩增个体上，即那些患有脆性X综合征（>200个CGG重复序列）、前突变（55 - 200个重复序列）或处于灰色区域（不同定义为45 - 54或41 - 54个重复序列）的个体。相比之下，WLS是一个独特的数据来源，它来自于对普通人群中未经过筛选的个体队列进行CGG重复序列长度检测的数据。WLS是1957年威斯康星州所有高三学生中三分之一的随机样本。最近一轮的数据收集是在2011年；因此，该研究跨越了50多年。2008年和2011年从该队列中69%的存活成员那里获取了唾液样本，并对其中的CGG重复序列进行了检测。除了一个例外，该队列所有成员的CGG重复序列长度均低于100（范围从7到84）。本研究评估了CGG重复序列数量与智商、大学毕业、绝经年龄、亲生孩子数量、生育一个有智力或发育障碍孩子以及成年期经历抑郁发作可能性之间的基因型 - 表型关联。研究探讨了线性和曲线效应。尽管效应大小较小，但在CGG重复序列长度与高中智商分数、大学毕业、亲生孩子数量、绝经年龄以及抑郁发作可能性之间发现了显著关联。然而，重复序列长度与生育一个被诊断患有智力和发育障碍疾病的孩子之间没有显著关联。这项研究展示了随着重复序列长度变化的一系列表型效应，并说明了如何利用由罕见遗传病（如脆性X综合征）引发的研究来探究普通人群中的基因型 - 表型关联。
