No association between FMR1 premutation and either ADHD or anxiety in 53,707 women undergoing genetic testing for family planning purposes.

IF 6.6 1区医学 Q1 GENETICS & HEREDITY

Genetics in Medicine Pub Date : 2025-04-04 DOI:10.1016/j.gim.2025.101428

Liraz Klausner, Shai Carmi, Shay Ben-Shachar, Noa Lev-El Halabi, Lina Basel-Salmon, Dana Brabbing Goldstein

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引用次数: 0

Abstract

Purpose: FMR1 premutation has been inconsistently associated with neuropsychiatric phenotypes, possibly due to ascertainment bias. We investigated the association between FMR1 premutation and attention deficit hyperactivity disorder (ADHD), anxiety, and other psychiatric disorders in large-scale population-based genetic carrier screening data.

Methods: We defined premutation as having 58-200 CGG repeats. Phenotypes were identified in linked electronic medical records via formal diagnoses or relevant medication purchases. As a positive control, we assessed premature ovarian insufficiency (POI) and elevated follicle-stimulating hormone (FSH) levels before the age of 40.

Results: Our study included 53,707 women, among them 464 premutation heterozygotes. The premutation status was associated with POI (hazard ratio [HR]: 4.08, 95% confidence interval [CI]: 2.16-7.72) and high FSH (HR: 3.43, 95% CI: 2.65-4.43) but not with ADHD (HR: 1.08; 95% CI: 0.75-1.56), anxiety (HR: 0.74; 95% CI: 0.53-1.04), anxiety and depression (HR: 0.86; 95% CI: 0.69-1.07), and other psychiatric disorders (HR: 1.22; 95% CI: 0.73-2.03). Our study was sufficiently powered to detect HR in the range approximately 1.5-2.

Discussion: No association was found between FMR1 premutation status and either ADHD or anxiety. While our study design avoided bias towards affected families, participants may be healthier than average, and small effects cannot be excluded.

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在53,707名接受计划生育基因检测的妇女中，FMR1预突变与ADHD或焦虑之间没有关联。

目的：FMR1 预突变与神经精神表型的相关性并不一致，这可能是由于确认偏倚造成的。我们在大规模人群基因携带者筛查数据中调查了 FMR1 预突变与注意缺陷多动障碍（ADHD）、焦虑和其他精神疾病之间的关联：我们将58-200个CGG重复序列定义为突变。表型是通过正式诊断或相关药物购买在关联的电子病历中确定的。作为阳性对照，我们评估了 40 岁前的过早卵巢功能不全（POI）和卵泡刺激素（FSH）水平升高的情况：我们的研究包括 53 707 名女性，其中 464 人为预突变杂合子。预突变状态与 POI（危险比 [HR]：4.08，95% 置信区间 [CI]：2.16-7.72）和高 FSH（HR：3.43，95% CI：2.65-4.43）相关，但与多动症（HR：1.08；95% CI：0.75-1.56）、焦虑（HR：0.74；95% CI：0.53-1.04）、焦虑和抑郁（HR：0.86；95% CI：0.69-1.07）以及其他精神障碍（HR：1.22；95% CI：0.73-2.03）。我们的研究有足够的证据检测出大约在 1.5-2.5 讨论范围内的 HR：我们没有发现 FMR1 预突变状态与多动症或焦虑症之间存在关联。虽然我们的研究设计避免了对受影响家庭的偏倚，但参与者可能比一般人更健康，因此不能排除微小的影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genetics in Medicine 医学-遗传学

CiteScore

15.20

自引率

6.80%

发文量

857

审稿时长

1.3 weeks

期刊介绍： Genetics in Medicine (GIM) is the official journal of the American College of Medical Genetics and Genomics. The journal''s mission is to enhance the knowledge, understanding, and practice of medical genetics and genomics through publications in clinical and laboratory genetics and genomics, including ethical, legal, and social issues as well as public health. GIM encourages research that combats racism, includes diverse populations and is written by authors from diverse and underrepresented backgrounds.